Orientador: Jaime Amaya-Farfán / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-21T17:15:26Z (GMT). No. of bitstreams: 1 Morato_PriscilaNeder_D.pdf: 813172 bytes, checksum: 96f9ce7da352faefcc39166ef5fe4fa9 (MD5) Previous issue date: 2012 / Resumo: As proteínas do soro do leite apresentam propriedades nutricionais e funcionais que influenciam a modulação de funções bioquímicas e fisiológicas.Estudos têm demonstrado que as proteínas do soro do leite (PSL), principalmente na forma hidrolisada (PSLH) possuem a capacidade de aumentar os níveis de glicogênio muscular. Considerando que a captação de glicose pela célula do músculo esquelético relaciona-se diretamente à atividade de proteínas transportadoras de glicose, este estudo se propôs realizar dois experimentos para conhecer os efeitos da PSL e da PSLH e de alguns dos seus produtos de hidrólise nos transportadores de glicose em músculos de ratos. No experimento 1, o objetivo foi verificar se o consumo de PSL e PSLH modulam a concentração de transportadores de glicose GLUT-1 e GLUT-4 na membrana plasmática (MP) de células musculares de animais sedentários e exercitados. Foram utilizados 48 ratos Wistar machos divididos em dois grupos: sedentários e exercitados, e cada um desses subdivididos em outros três, de acordo com a dieta, totalizando 6 grupos (n=8 por grupo). Os animais foram mantidos por 9 dias recebendo as dietas experimentais baseadas na AIN-93G, com as seguintes fontes protéicas: caseína (CAS), utilizada como controle, proteína do soro do leite (PSL), proteína do soro do leite hidrolisada (PSLH), e o animais exercitados foram submetidos a uma única sessão de exercício a 15m/min durante 60min um dia anterior ao sacrifício. Após o período experimental os animais foram sacrificados, os transportadores de glicose no músculo, GLUT-1 e GLUT-4, foram analisados por western blot. Adicionalmente, glicogênio, aminoácidos livres plasmáticos, insulina e indicadores bioquímicos de saúde foram determinados por métodos padrões. O consumo de PSLH elevou significativamente as concentrações de GLUT-4 na MP e de glicogênio, enquanto GLUT-1, insulina e os indicadores de saúde não apresentaram alterações. Baseado nas evidências do experimento 1, de que o consumo de PSLH eleva os estoques de glicogênio muscular e que também aumenta a concentração do transportador de glicose GLUT-4 na membrana plasmática, o experimento 2 teve como objetivo identificar quais componentes da PSLH poderiam modular a translocação do transportador de glicose GLUT-4 para a MP em músculo esquelético. Foram utilizados 49 ratos Wistar machos divididos em 7 grupos (n=7), que receberam soluções orais de glicose 30% mais 0,55 g/kg de peso corpóreo os seguintes componentes da PSLH: a) glicose (controle); b) PSLH; c) L-isoleucina; d) L-leucina; e) L-leucina mais L-isoleucina; f) peptídeo Lisoleucil- L-leucina; g) peptídeo L-leucil-L-isoleucina. Após receberem as soluções, os animais foram sacrificados, o transportador de glicose GLUT-4 no músculo foi analisado por western blot. Também foram analisados glicogênio, glicemia, insulina, aminoácidos livres plasmáticos e musculares, e indicadores bioquímicos de saúde por métodos clássicos. Entre os componentes testados da PSLH, o peptídeo leucil-isoleucina e o aminoácido isoleucina se mostraram mais eficientes em translocar GLUT-4 para a MP, favorecendo a captação de glicose pelo músculo esquelético. Os resultados obtidos nos experimentos indicam que o consumo da PSLH e de seus componentes ao aumentarem a translocação de GLUT-4 para a membrana plasmática, poderiam auxiliar no tratamento ou prevenção do diabetes do tipo II / Abstract: The milk whey proteins (WP) exhibit nutritional and functional properties which result in the modulation of the biochemical and physiological functions. Studies have shown that the WP, especially those in the hydrolyzed form (WPH),has the capacity to increase muscle glycogen levels. Considering that glucose uptake by the skeletal muscle cell is directly related to the activity of the glucose transporter proteins, the present study proposed to carry out two experiments to determine the effects of WP and WPH and of some of their hydrolysis products on the glucose transporters in rat muscles. The objective of experiment 1 was to verify if the consumption of WP and WPH are able to modulate the concentration of the glucose transporters GLUT-1 and GLUT-4 in the plasma membrane (PM) of muscle cells in sedentary and exercised animals. Forty-eight male Wistar rats were used, divided into sedentary and exercised groups, each of which was sub-divided into three sub-groups according to the diet, giving a total of 6 groups (n=8 per group). The animals were maintained for 9 days on experimental diets based on AIN-93G with the following protein sources: casein (CAS) used as the control, whey protein (WP) and whey protein hydrolysate (WPH). The exercised animals were submitted to a single exercise session for 60 min at 15m/min one day prior to euthanasia. After the experimental period, the animals were euthanized, and the muscle glucose transporters GLUT-1 and GLUT-4 analyzed by western blot. In addition, glycogen, free plasma amino acids, insulin and the biochemical health indicators were analyzed by standard techniques. The consumption of WPH significantly increased the concentrations of GLUT-4 in the PM and of glycogen, whereas GLUT-1, insulin and the health indicators remained unaltered. Based on evidence from experiment 1 that the consumption of WPH raised the muscle glycogen reserves and also the concentration of the glucose transporter GLUT-4 in the plasma membrane, the second experiment was designed to identify which WPH components could modulate translocation of the glucose transporter GLUT-4 to the PM in the skeletal muscle of the animals. Forty-nine male Wistar rats were used, divided into 7 groups (n=7), who were orally fed 30% glucose solutions plus 0.55 g/kg of body weight of the following WPH components: a) glucose (control); b) WPH; c) L-isoleucine; d) L-leucine; e) L-leucine plus L-isoleucine (50:50 mixture of both amino acids); f) L-isoleucyl-L-leucine peptide or g) L-leucyl-L-isoleucine peptide. After receiving the solutions, the animals were euthanized and the GLUT-4 determined by western blot. Glycogen, glycemia, insulin, free plasma and muscle amino acids, and the biochemical health indicators were also analyzed by classical methods. Of the WPH components tested, the peptide L-leucyl-L-isoleucine and the amino acid L-isoleucine were shown to be more efficient in translocating GLUT-4 to the PM, favoring the capture of glucose by the skeletal muscle. The results obtained from these experiments indicated that the consumption of WPH and its components increased GLUT-4 translocation to the plasma membrane, and could aid in the treatment and prevention of type ll diabetes / Doutorado / Nutrição Experimental e Aplicada à Tecnologia de Alimentos / Doutora em Alimentos e Nutrição

Le développement des nouvelles technologies de l'information et de la communication nécessite la miniaturisation et l'intégration des dispositifs optiques. La plasmonique, qui utilise des nanostructures métalliques pour manipuler la lumière à l'échelle nanométrique, permet la réalisation de dispositifs optiques jusqu'à des limites ultimes. Le but de la présente étude est de concevoir et de fabriquer des nanoarchitectures complexes qui peuvent être incorporées dans différents dispositifs plasmoniques capables de guider la lumière de manière active. Diverses nanostructures d'or, telles que des nanotriangles d'or creux ou des nanotripodes enrobés d'or, ont été synthétisés et assemblés en utilisant des liens moléculaires ou un origami d'ADN. Les propriétés optiques des nanodispositifs fabriqués ont été étudiées afin de démontrer leur capacité à guider la lumière. / The development of new information and communication technologies requires the miniaturization and integration of optical devices. Plasmonics, a field of optics that utilizes metallic nanostructures to manipulate light at the nanoscale, enables the scaling of optical devices down to ultimate limits. The purpose of the present study is to design and fabricate complex nanoarchitectures that can be incorporated into different plasmonic devices able to guide light in an active way. Various gold nanostructures, such as hollow gold nanotriangles or gold coated nanotripods, were synthesized and assembled using molecular linkers or a DNA origami template. The optical properties of the fabricated nanodevices were investigated in order to evidence their ability to guide light.

Cette thèse est consacrée à l’étude du transport branché, de problèmes variationnels qui y sont liés et de structures fractales qui peuvent y apparaître. Le problème du transport branché consiste à connecter deux mesures de même masse par le biais d’un réseau en minimisant un certain coût, qui sera pour notre étude proportionnel à mLα afin de déplacer une masse m sur une distance L. Plusieurs modèles continus ont été proposés pour formuler le problème, et on s’intéresse plus particulièrement aux deux grands types de modèles statiques : le modèle Lagrangien et le modèle Eulérien, avec une emphase sur le premier. Après avoir posé proprement les bases de ces modèles, on établit rigoureusement leur équivalence en utilisant une décomposition de Smirnov des mesures vectorielles à divergence mesure. On s’intéresse par la suite à un problème d’optimisation de forme lié au transport branché qui consiste à déterminer les ensembles de volume 1 les plus proches de l’origine au sens du transport branché. On démontre l’existence d’une solution, décrite comme un ensemble de sous-niveau de la fonction paysage, désormais standard en transport branché. La régularité Hölder de la fonction paysage, obtenue ici sans hypothèse de régularité a priori sur la solution considérée, permet d’obtenir une borne supérieure sur la dimension de Minkowski de son bord, qui est non-entière et dont on conjecture qu’elle en est la dimension exacte. Des simulations numériques, basées sur une approximation variationnelle à la Modica-Mortola de la fonctionnelle du transport branché, ont été effectuées dans le but d’étayer cette conjecture. Une dernière partie de la thèse se concentre sur la fonction paysage, essentielle à l’étude de problèmes variationnels faisant intervenir le transport branché en ce sens qu’elle apparaît comme une variation première du coût d’irrigation. Le but est d’étendre sa définition et ses propriétés fondamentales au cas d’une source étendue, ce à quoi l’on parvient dans le cas d’un réseau possédant un système fini de racines, par exemple pour des mesures à supports disjoints. On donne une définition satisfaisante de la fonction paysage dans ce cas, qui vérifie en particulier la propriété de variation première et on démontre sa régularité Hölder sous des hypothèses raisonnables sur les mesures à connecter. / This thesis is devoted to the study of branched transport, related variational problems and fractal structures that are likely to arise. The branched transport problem consists in connecting two measures of same mass through a network minimizing a certain cost, which in our study will be proportional to mLα in order to move a mass m over a distance L. Several continuous models have been proposed to formulate this problem, and we focus on the two main static models : the Lagrangian and the Eulerian ones, with an emphasis on the first one. After setting properly the bases for these models, we establish rigorously their equivalence using a Smirnov decomposition of vector measures whose divergence is a measure. Secondly, we study a shape optimization problem related to branched transport which consists in finding the sets of unit volume which are closest to the origin in the sense of branched transport. We prove existence of a solution, described as a sublevel set of the landscape function, now standard in branched transport. The Hölder regularity of the landscape function, obtained here without a priori hypotheses on the considered solution, allows us to obtain an upper bound on the Minkowski dimension of its boundary, which is non-integer and which we conjecture to be its exact dimension. Numerical simulations, based on a variational approximation a la Modica-Mortola of the branched transport functional, have been made to support this conjecture. The last part of the thesis focuses on the landscape function, which is essential to the study of variational problems involving branched transport as it appears as a first variation of the irrigation cost. The goal is to extend its definition and fundamental properties to the case of an extended source, which we achieve in the case of networks with finite root systems, for instance if the measures have disjoint supports. We give a satisfying definition of the landscape function in that case, which satisfies the first variation property and we prove its Hölder regularity under reasonable assumptions on the measures we want to connect.

Dans cette thèse, nous concevons des approximations par champ de phase de certains problèmes de Transport Branché. Le Transport Branché est un cadre mathématique pour modéliser des réseaux de distribution offre-demande qui présentent une structure d'arbre. En particulier, le réseau, les usines d'approvisionnement et le lieu de la demande sont modélisés en tant que mesures et le probléme est présenté comme un probléme d'optimisation sous contrainte. Le coût de transport d'une masse m le long d'un bord de longueur L est h(m)xL et le coût total d'un réseau est défini comme la somme de la contribution sur tous ses arcs. Le cas du Transport Branché correspond avec la choix h(m) =|m|^α où α est dans [0,1). La sous-additivité de la fonction cout s'assure que déplacer deux masses conjointement est moins cher que de le faire séparément. Dans ce travail, nous introduisons diverses approximations variationnelles du problème du transport branché. Les fonctionnelles que on vais utiliser sont basées sur une représentation par champ de phase du réseau et sont plus lisses que le problème original, ce qui permet des méthodes d'optimisation numérique efficaces. Nous introduisons une famille des fonctionnelles inspirées par le fonctionnelle de Ambrosio et Tortorelli pour modéliser une fonction de coût h affine dans l'espace R^2. Pour ce cas, nous produisons un résultat complet de Gamma-convergence et nous le corrélons avec une procédure de minimisation alternée pour obtenir des approximations numériques des minimiseurs. Puis nous généralisons cette approche à n'importe quel espace R^n et obtenons un résultat complet de $Gamma$-convergence dans le cas de surfaces k-dimensionnelles avec k<n. En particulier, nous obtenons une approximation variationnelle du problème du Plateau dans n'importe quelle dimension et co-dimension. Dans la dernière partie de la thèse, nous proposons deux approches générales pour des fonctions de coût concave. Dans le premier, nous introduisons une approche par plusieurs champs de phase et récupérons n'importe quelle fonction de coût affine par morceaux. Enfin, nous proposons et étudions une famille de fonctions permettant d'obtenir dans la limite toutes fonction de coût concave h. / In this thesis we devise phase field approximations of some Branched Transportation problems. Branched Transportation is a mathematical framework for modeling supply-demand distribution networks which exhibit tree like structures. In particular the network, the supply factories and the demand location are modeled as measures and the problem is cast as a constrained optimization problem. The transport cost of a mass m along an edge with length L is h(m)xL and the total cost of a network is defined as the sum of the contribution on all its edges. The branched transportation case consists with the specific choice h(m)=|m|^α where α is a value in [0,1). The sub-additivity of the cost function ensures that transporting two masses jointly is cheaper than doing it separately. In this work we introduce various variational approximations of the branched transport optimization problem. The approximating functionals are based on a phase field representation of the network and are smoother than the original problem which allows for efficient numerical optimization methods. We introduce a family of functionals inspired by the Ambrosio and Tortorelli one to model an affine transport cost functions. This approach is firstly used to study the problem any affine cost function h in the ambient space R^2. For this case we produce a full Gamma-convergence result and correlate it with an alternate minimization procedure to obtain numerical approximations of the minimizers. We then generalize this approach to any ambient space and obtain a full Gamma-convergence result in the case of k-dimensional surfaces. In particular, we obtain a variational approximation of the Plateau problem in any dimension and co-dimension. In the last part of the thesis we propose two models for general concave cost functions. In the first one we introduce a multiphase field approach and recover any piecewise affine cost function. Finally we propose and study a family of functionals allowing to recover in the limit any concave cost function h.

Depuis quelques années, une nouvelle gamme de matériaux polyamides hautes performances voit le jour pour des secteurs clés comme l’automobile. Par exemple, ces nouveaux matériaux sont destinés grâce à leur faible densité à alléger les pièces et donc à réduire la consommation de carburant. Les propriétés recherchées sont avant tout une grande stabilité dimensionnelle, une résistance aux hautes températures et une mise en forme facile. L’objectif est la synthèse de ces copolyamides obtenus à partir d’une diamine aliphatique, d’un amino-acide d’origine renouvelable et d’acide téréphtalique. Une augmentation du taux de 6.T au sein du système 11/6.T entraîne alors une augmentation des caractéristiques thermiques mais une perte des propriétés mécaniques. Pour pallier cela, l’objectif suivant est l’amélioration de la ductilité du copolymère en abaissant la température de transition vitreuse mais en gardant des propriétés thermiques élevées. L’intérêt s’est porté sur l’ajout de comonomères ramifiés au sein du système étudié pour agir par plastification interne. Ainsi, l’ajout de comonomères au sein du système entraîne une amélioration des propriétés mécaniques avec une légère baisse du module de traction et une augmentation de l’allongement à la rupture. De plus, il a été mis en évidence une diminution de la reprise en eau lors de l’augmentation du taux molaire de comonomères au sein du système. En conclusion, l’introduction des comonomères permet d’obtenir des nouveaux polyphtalamides avec des propriétés thermiques élevées et des propriétés mécaniques et de reprise en eau améliorées par effet de plastification interne. / In recent years, a new class of crystalline polyamides has been commercialized. These materials known as polyphthalamides contain aromatic groups in the polymer backbone. The aim of the project is to obtain polyphthalamides from raw materials of renewable origin. So, in addition to the aromatic group(s), polyphthalamides are synthesized from an aliphatic diamine and a long-chain monomer of renewable origin. The objectives are to provide novel semi-crystalline, melt processible, partially aromatic copolyamides with high melting point, high glass transition temperatures, low moisture absorption and high dimensional stability. In this study, polyphthalamides with a variable amount of 11 (derived from condensation of 11-amino undecanoic acid) and 6,T units (derived from condensation of hexamethylene diamine and terephthalic acid) are synthetized and it is tried to assess, using thermal analysis, the effect of 6,T units content on the melting point (Tm) and glass transition temperature (Tg) of the resultant copolyamides. As the 6,T unit content is increased, crystalline copolyamides are obtained having a high melting point and a high glass transition temperature. Characterization of molar mass is also performed to check the progress of the synthesis. This work points out that the addition of 6,T units to linear polyamides increases thermal properties. Another possibility can be the addition of various other branched monomers to evaluate their influence on mechanical and thermal properties. The aim is to keep high thermal properties with improving the ductibility of copolyamides. These branched comonomers will act as intern plasticizers. The increase of the comonomers amount in copolymers drives to an improvement of mechanical properties and a decrease of water absorption.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20225号 / 医博第4184号 / 新制||医||1019(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 Shohab YOUSSEFIAN, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13558号 / 論医博第2287号 / 新制||医||1067(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩田 想, 教授 中川 一路, 教授 妹尾 浩 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Yes / The shape memory effect of highly oriented long‐chain‐branched poly(lactic acid) (LCB‐PLA) prepared through solid‐phase die drawing technology was studied by comparison with PLA. When the recovery temperature increased from 60°C to 120°C, for PLA, only one‐step recovery at about 80°C can be observed and the recovery ratio was below 21.5%, while, for LCB‐PLA, multiple recovery behavior with high recovery ratio of 78.8% can be achieved. For oriented PLA, the recovery curve of the final sample showed the same trend with that of sample suffering just free drawing; while for oriented LCB‐PLA, the recovery curve of the final sample showed the same trend with that of sample suffering just die drawing. After shape recovery, the mechanical properties of LCB‐PLA showed a linear downward trend with the recovery temperature. Together with amorphous phase, the oriented mesomorphic phase, which formed during solid die drawing, can act as switching domains. And thus, upon heating, the chain segment of amorphous phase relaxed at first and triggered the first macroscopical shape recovery, leading to the decrease of long period (Lac) and the thickness of the amorphous layer (La). Then, with further increasing temperature, the oriented mesomorphic phase gradually relaxed resulting subsequently multi‐shape recovery, and the Lac and the La further decreased. Therefore, by regulating the recovery temperature of oriented LCB‐PLA, the shape recovery ratio and mechanical strength can be controlled effectively, and thus the self‐reinforced and self‐fastening effect can be achieved simultaneously for PLA as bone fixation material.

Morphological development during crystallization of thin films of poly(ethylene oxide) (PEO) / poly(methyl methacrylate) (PMMA) blends has been reported. Studies have focused on the effects of the blend composition, PMMA molecular weight, film thickness, and crystallization temperature on the observed crystal morphology. As the blend composition was varied from 90 to 30 wt% PEO, the crystal morphology varied from spherulites to needles and dendrites. Variation of the crystallization temperature and PMMA molecular weight resulted in similar changes in morphology. A morphological map demonstrating the roles of the experimental controls on the observed crystal morphology has been developed. This map was used as a tool for more detailed studies of the observed morphologies and morphological transitions. The dendritic region of the map (~ 30 = 40 wt% PEO) was studied in detail. Changes in the diffusion length were achieved through variation of the PMMA molecular weight, and were shown to influence the secondary sidebranch spacing. Sidebranch spacing measurements revealed that coarsening of the dendritic microstructure occurred well after the competition between diffusion fields of neighboring dendrite arms vanished, indicating the existence of another coarsening mechanism. These studies of dendritic sidebranching indicate that polymer dendrites develop by mechanisms similar to those in small molecules and metals. A number of in-situ observations of morphological transitions have also been reported, including a dense-branched morphology (DBM)/dendrite transition, a DBM/stacked-needle/needle transition, and a transition from dendrites with 90o sidebranching to dendrites with 45o branching or a dense-branched morphology, both of which grow at 45o to the original dendrite trunk. The DBM/dendrite transition occurred over a range of crystallization temperatures, indicating that the transition is not sharp. Crystal growth rate measurements verified this result. The DBM/stacked-needle/needle transitions demonstrated distinct jumps in the crystal growth rate, indicating a change in the growth mechanism or direction. For the transition involving a change in the growth direction, the effective level of noise (fluctuation) was found to be important in morphological selection. The results of this work have helped to define new directions for the study of crystal morphologies, especially in the areas of spherulite formation and dendritic growth. / Ph. D.

Binding of the Rev protein with Rev Response Element (RRE) RNA present in singly- and unspliced mRNA transcripts is necessary for the replication of HIV-1. This interaction transports the mRNA transcripts from the nucleus to the cytoplasm for translation of the necessary structural and enzymatic proteins for the newly budding virus as well as for providing its genetic material. Given the high rate of mutation in HIV-1, the highly conserved and pertinent RRE RNA is of high interest for pharmaceutical intervention. Consequently, a branched peptide library containing unnatural amino acids was developed to target RRE RNA with the goal of increasing stability, potency, selectivity, and in vivo activity for RRE RNA. An unnatural amino acid branched peptide library (46,656 sequences) was synthesized and screened against RRE IIB and several hits in the sub-micromolar regime were found. A number of hits demonstrated selectivity in the presence of other RNAs in addition to two hits, 4A5 and 4B3, significantly inhibiting HIV-1 growth in vitro. These peptides inhibited HIV-1 replication in a concentration dependent manner and were demonstrated to be non-toxic. Further analysis of 4A5 and 4B3 via footprinting and SHAPE-MaP experiments determined that these peptides blocked binding of Rev through binding at the primary and secondary binding sites of RRE RNA. Sphingosine 1-phosphate (S1P) is a signaling molecule that plays a role in various biological processes including immunity, neurogenesis, and angiogenesis. The role S1P plays is largely determined by its location, in which Spinster homolog 2 (spns2) and mfsd2b are the two known transporters. The two transporters exist in different cell types and cellular localizations, with spns2-produced S1P being responsible for trafficking of lymphocytes. As such, spns2 has become of interest for therapeutic targeting in autoimmune and inflammatory diseases. To validate spns2 as a target in pharmaceutical intervention, a series of spns2 inhibitors were developed. A screening of a library of inhibitors found that compound SLP7120922 demonstrated inhibition of spns2 transport activity. The design, synthesis, and biological evaluation of inhibitors based on SLP7120922 is described. Modifications to the lipophilic tail region were performed with one compound 4.40f discovered to be potent, minimally toxic, and active in vivo. A series of modifications to the head region were then conducted that evaluated linear head derivatives with alkyl-, amide-, and amino acid-based groups. A number of compounds are reported that demonstrate good in vitro activity and minimal toxicity with two compounds, 4.48b and 4.52c, showing favorable in vivo activity in mice. / Doctor of Philosophy / Human immunodeficiency virus (HIV-1) has a high rate of mutation, which commonly leads to the need for many types of medications throughout the lifetime of a patient. In order to design a therapeutic that the virus has a low chance of growing resistance to, a target needs to be chosen with a low mutation rate. One such target is the Rev Response Element (RRE) RNA and it is necessary for the virus to replicate. A protein named Rev binds to RRE RNA in order for RRE to carry out its pertinent function. To block this function we have chosen branched peptides to target the RNA. Peptides are made of the same building blocks of proteins, but are much shorter than proteins. The peptides described here are made up of modified building blocks, called unnatural amino acids. This work describes the generation of an unnatural amino acid branched peptide library and how it was screened in order to find branched peptides that bind RRE RNA. Many peptides were found to bind RRE RNA but two in particular, 4A5 and 4B3, were the best binders that inhibited HIV-1 growth. The remainder of the work describes how these peptides bind to RRE RNA, while demonstrating that they are non-toxic and bind HIV-1 in a concentration dependent manner. A transporter protein termed Spinster homolog 2 (spns2) transports a signaling molecule known as sphingosine 1-phosphate (S1P). For our immune system to function properly, spns2 has to transport S1P to the appropriate places to signal to immune cells. Unfortunately, this is a problem in autoimmune and inflammatory diseases, such as multiple sclerosis, due to these diseases having an overactive immune system. A potential way to treat these diseases would be by inhibiting spns2. This work describes the design, synthesis, and biological evaluation of spns2 inhibitors. Many compounds were found to inhibit spns2 to a degree, but three compounds, in particular, show potent and effective inhibition in mice.