超級混合圖是一個 H = (X,C,D) 的表示法，其中X是代表點集合，而C和D是X的部分子集合，稱為邊。一個嚴格k種顏色可著色法指的是由X的點集對應到{1,2,…,k}的一種關係，其中C代表每一個C邊至少有兩個點同色，而D代表每一個D邊至少有兩個點不同色。C和D都有可能是空集合。假如超過(少於)k並沒有可著色的方法數，則k稱為最大著色數(最小著色數)。而H的每個邊都恰好有r個點則稱為r均勻超級混合圖。 對於r均勻C超級混合圖，如果限定了最大著色數大於等於k的話，則將會改變最大著色數的邊數。如果要找出滿足此條件的最大著色數的最大的邊數，我們主要區分成三種不同的情形來討論，分別是r比k大、r比k小和r = k。 / A mixed hypergraph is a triple H = (X, C,D), where X is the vertex set, and each of C,D is a list of subsets of X. A strict k-coloring is a onto mapping from X to {1,2, . . . , k} such that each C ∈ C contains two vertices have a common value and each D ∈ D has two vertices have distinct values. Each of C,D may be empty. The maximum(minimum) number of colors over all strict k-colorings is called the upper(lower) chromatic number of H and is denoted by χ^¯(H)(χ(H)). If a hypergraph H has no multiple edges and all its edges are of size r, then H is called an r-uniform hypergraph. We want to find the maximum number of edges for r-uniform C-hypergraph of order n with the condition χ^¯(H) ≥ k, where k is fixed. We will solve this problem according to three different cases, r < k, r = k and r > k.

With the prevalence of legacy C/C++ code, issues of readability and maintainability have become increasingly important. When we consider the problem of refactoring or migrating C/C++ code, we see the significant role that preprocessor directives play. It is partially because of these preprocessor directives that code maintenance has become extremely difficult. This thesis describes a method of fact extraction and code manipulation to create a set of transformations which will remove preprocessor directives from the original source, converting them into regular C/C++ code with as few changes as possible, while maintaining readability in the code. In addition, some of the subtle issues that may arise when migrating preprocessor directives are explored. After discussing the general architecture of the test implementation, an examination of some metrics gathered by running it on two software systems is given.

L'une des principales cibles pour la thérapie visant le virus de l'hépatite C (VHC) est l'ARN polymérase dépendante de l'ARN NS5B indispensable à la réplication du génome virale. NS5B est l'une des enzymes clefs du cycle virale de VHC et son activation met en jeu aussi bien des interactions intramoléculaires que des interactions avec des cofacteurs viraux et cellulaires au sein du complexe de réplication. Nous avons développé une nouvelle stratégie d'inhibition de NS5B basée sur l'élaboration de peptides courts dérivés de motifs exposés à la surface de l'enzyme dans le but de cibler les nombreuses interactions impliquées dans l'activation de cette protéine. En associant une analyse fine de la structure cristallographique de NS5B avec de la modélisation moléculaire, nous avons élaboré des peptides courts mimant les motifs « hotspot » de la protéine. Ces peptides ont été évalués sur système réplicon de génotype 1b et nous avons ainsi identifié un peptide leader Moon1 de 15 résidus correspondant à un motif hautement conservé du domaine "thumb". Dans ce travail, nous avons étudié en détail la structure et le mécanisme moléculaire de ce nouvel inhibiteur de NS5B. Moon1 inhibe l'activité polymérase de la forme sauvage de NS5B ainsi que celle de mutants résistants au inhibiteurs nucléosidiques et non nucléosidiques. Nous avons démontré que la fixation de Moon1 entraine un changement de conformation de NS5B et se fait préférentiellement avec NS5B dans une conformation fermée. Ce peptide inhibe spécifiquement l'interaction entre NS5B et l'ARN double brin, indépendamment de la présence d'ions métalliques et de manière dose-dépendante. Moon1 bloque la transition entre l'étape d'initiation de novo de la synthèse d'ARN et l'extension du primer. Nous avons démontré que les résidus essentiels à l'activité de Moon1 sont hautement conservés à travers les différents génotypes et sous-types de VHC. De plus, nous avons établi une séquence minimale pour l'activité de Moon1. Nos travaux permettent de valider l'intérêt d'une stratégie interfaciale ciblant une enzyme clef du cycle du VHC et les interactions intra et intermoléculaires nécessaires à son activation. / The non-structural protein RNA-dependent RNA polymerase (RdRp) NS5B plays a key role in hepatitis C virus (HCV) replication and is currently considered as one of the most relevant target to develop safe anti-HCV agents. Although many small molecules have been identified as inhibitors of NS5B, very few are active in clinic. The structure and function of NS5B have been well characterized and as other polymerases, NS5B adopts a typical “right-hand” conformation containing the characteristic fingers, palm and thumb subdomains. The activation of NS5B requires conformational changes involving intramolecular contacts as well interactions with viral proteins and host factors in the replication complex. We developed a new strategy for NS5B inhibition based on short interfacial peptides derived from NS5B surface accessible motifs that target protein-protein interfaces or essential motifs involved in NS5B-activation. Combining the NS5B crystallogaphic structure and molecular modelling, we have designed short peptides derived from NS5B surface “hotspots” that were screened using HCV genotype 1b replicon cell system. We have identified Moon1, a short 15-residu peptide, derived from a well-conserved motif located in the NS5B thumb domain that inhibits HCV replication in the low nanomolar range. Moon1 tightly binds NS5B in a conformational-dependent manner and induces NS5B conformational changes. This peptide specifically inhibits double-stranded RNA/NS5B interactions in a dose-dependent and metal ions-independent manner. Moon1 blocks the transition between RNA de novo initiation and primer-extension. We showed that residues required for Moon-1 anti-polymerase activity are well-conserved among HCV genotypes and subtypes and a minimal Moon1 active motif was established. Taken together, these results demonstrate that NS5B structural dynamics constitute an attractive target for HCV chemotherapeutics and for the design of more specific new antiviral drugs.

Le premier volet de cette thèse porte sur la synthèse de thionoesters linéaires dans le but, à terme, d'obtenir des spiro-orthoesters dérivés de sucres. Comme les esters modèles synthétisés n'ont pu être transformés en thionoesters via les réactions classiques, une nouvelle voie à partir du thiosphogène a été envisagée. Cependant, une des étapes s'est montrée impossible à réaliser, ce qui a conduit à l'abandon de ce projet.La seconde partie de ce manuscrit concerne la synthèse de précurseurs du C-KRN 7000. Le but était de synthétiser un époxyaldéhyde hautement fonctionnalisé. Une première synthèse effectuée à partir du D-ribose a permis d'obtenir séparément l'aldéhyde et l'époxyde, mais les deux fonctions n'ont pu être réunies sur une même molécule. Toutefois, une méthode originale d'inversion de configuration, ainsi qu'une étape de dihydroxylation asymétrique sélective ont pu être mises aupoint, permettant d'accéder à des synthons chiraux hautement fonctionnalisés. Une seconde voie d'accès à partir du D-galactose a été débutée, mais n'a pu être menée à terme faute de temps.Parallèlement à cela, un autre précurseur acétylénique a pu être obtenu, lui aussi à partir du D-ribose. / The first part of this work focuses on the synthesis of linear thionoesters in order to obtain sugar derived spiro-orthoesters. Failure to transform the synthetised model esters into thionoesters via classical reactions lead to the development of a new method starting from thiophosgene. This project was not completed due to one step in the reaction sequence that proved to be unachievable.The second part of this manuscript deals with the synthesis of C-KRN 7000 precursors. The purpose was to synthesize a highly functionalized epoxyaldehyde. A first synthesis starting from D-ribose led to the aldehyde and epoxyde separately, but both functions couldn't be united in the same molecule. However, an original method for inversion of configuration, and a selective asymmetric dihydroxylation step were developed, providing access to highly functionalised chiral synthons. A second path from D-galactose was initiated, but wasn't completed due to time constraints. Another alkyne precursor was synthesized, also from D-ribose.

In 1803, the Louisiana Purchase doubled the territory of the fledgling United States. Taking control of and defending the new territory, especially the culturally heterogeneous city of New Orleans occupied much of the administration's time. Most of the burden for establishing the defense policy rested on William C. C. Claiborne, a staunch Jeffersonian, former member of Congress from Tennessee, and previous governor of the Mississippi Territory. By working with local business leaders with a stake in American success, observing the local customs and traditions, and gradually encouraging political participation, Claiborne successfully introduced the American militia system to a culture far different from that of his native Virginia. Claiborne's policies reduced the likelihood that local dissidents and foreign powers such as Spain and Great Britain could conspire to subvert American government in Louisiana by rebellion and invasion.

Phospholipase Cε (PLCε) is a member of the PLC family of enzymes, which hydrolyze phosphatidylinositol lipids following the activation of G protein coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). PLCε is unique among the PLC superfamily as it contains an N-terminal CDC25 domain, which has a guanine nucleotide exchange factor (GEF) activity for the small G protein Rap1A, and two C-terminal Ras association (RA) domains that bind scaffolding proteins and activated G proteins. PLCε activity plays an important role in cardiomyocyte contractility and survival. The best-characterized pathway of PLCε activation is mediated by β-adrenergic (β-AR) receptors. Stimulation of these receptors culminates in the activation of the small GTPase Rap1A, which binds to PLCε at the sarcoplasmic reticulum. There, PLCε hydrolyzes phosphatidylinol-4-phosphate (PI₄P) to produce diacylglycerol (DAG). Prolonged activation of this pathway results in increased Ca²⁺-induced Ca²⁺ release (CICR) and increased expression of hypertrophy-related genes. However, the structural basis of PLCε basal activity, and the mechanism of Rap1A activation are largely unknown. We have now obtained the first high-resolution structure of PLCε. These studies, together with biochemical validation of our structure-based hypotheses, provide the first molecular insights into this enzyme.

Obwohl die Geschichte der Kindheit seit Jahrhunderten auch mit Kindesbestrafung, Kindesmisshandlung und sogar Kindstötung verbunden ist, definierten erst Ende der 40er Jahre zunächst J. Caffey und F. N. Silverman, in den 60er Jahren jedoch vor allem H. Kempe und R. E. Helfer das Krankheitsbild des „battered child“ mit den Trias: • radiologisch nachweisbare subperiostale Blutungen mit Verkalkungen, Frakturen und traumatischen Gelenkabsprengungen • Subduralergüssen und • Retinablutungen. Diese Symptome mögen in ihrer Gesamtheit zwar spezifisch für eine traumatische Einwirkung sein, doch ist eine detaillierte, insbesondere radiologische Diagnostik zum Ausschluss anderer Leiden von großer Wichtigkeit. Eine medizinhistorische Aufarbeitung der ersten pädiatrischen Röntgenbilder zwischen 1895 und 1910 zeigt, dass ein damals häufig diagnostiziertes Krankheitsbild die Möller-Barlow Krankheit war, die erstmal von J. Möller im Jahre 1859 beschrieben wurde. Schon damals galt sie überwiegend als Vitamin-C-Mangelerkrankung des Säuglings und Kleinkindes, die sich klinisch vor allem in Form einer hochgradigen Berührungsempfindlichkeit sowie Extremitätenschwellungen äußerte. Dies konnten C. Hart und O. Lessing durch Tierexperimente bestätigten. Dank ihrer, sowie auch J. Schoedels, C. Nauwercks und C. Schmorls vielzähliger makro- und mikroskopischer Studien konnten die charakteristischen Befunde • verkalkte subperiostale Blutungen • metaphysäre Trümmerfeldzonen • zentrale Osteoporose und • Verbreiterung und Auftreibung der Knorpel-Knochen-Grenzen erhoben werden. Schon damals wiesen jedoch bedeutende Kinderärzte wie O. Heubner darauf hin, dass die wirkliche Pathophysiologie erst unzureichend geklärt sei. Seit 1915 wurden kaum weitere Original-Kasuistiken publiziert und heute wird das Krankheitsbild nur noch in Einzelfällen beobachtet. Eine Bewertung der vor 1910 angefertigten Röntgenbilder von Kindern, bei denen M.-B. Krankheit diagnostiziert wurde, lässt keinen einheitlichen Befund erheben und zumindest ein Teil der pathologischen Auffälligkeiten könnte aus heutiger Sicht durchaus als Folge traumatischer Einwirkungen im Sinne eines Schütteltraumas mit subperiostalen Blutungen interpretiert werden. Die Tierexperimente weisen aber auch darauf hin, dass ein exzessiver Vitamin-C-Mangel subperiostale Hämorrhagien entstehen lassen. Des Weiteren lassen die bei der M.-B. Krankheit beschriebenen Röntgenveränderungen auch eine Vielzahl von Differentialdiagnosen zu, wie z. B. die Rachitis, das Menkes-Syndrom, die Lues connata, die Osteogenesis imperfecta, die akute Leukämie und vor allem die Kindesmisshandlung. Resümierend sollte die Erstbeschreibung radiologischer Veränderungen des typischen Schütteltraumas im Säuglings- und Kleinkindesalter um mindestens 50 Jahre vorverlegt und die M.-B. Krankheit vor allem als medizinhistorisches Phänomen differenter Ursache angesehen werden. Radiologische Veränderungen in Form subperiostaler Blutungen, Verkalkungen und einer gestörten Ossifikation sind in erster Linie als Folgen eines Schütteltraumas anzusehen, doch sollte bei der Differentialdiagnostik auch an Ernährungsstörungen mit Vitamin-C-Mangel gedacht werden. / Although the history of childhood is associated with child abuse, punishment and even killing of children, first J. Caffey and F. N. Silverman in the forties and H. Kempe and R. E. Helfer in the sixties defined the battered child syndrome with the trias: • subperiostal haemorrhage with calcification, fractures and articular divulsion • subdural extravasation and • retinal bleeding. A medical-historical evaluation of the first paediatric roentgenographies between 1895 and 1910 shows an often diagnoses clinical picture: the Möller-Barlow disease, which seemed to be a vitamin c deficiency disease in infants. Typical findings were calcified subperiostal haemorrhage, metaphyseal comminuted zone and widening of the chondro-osseous zone. The radiographic findings from children who suffered from Möller-Barlow disease could be also due to child abuse or other differential diagnosis such as rickets, Menkes-syndrome, Lues connata, osteogenesis imperfecta or acute leukaemia. To sum up, the first description of radiographic alterations in abused infants should brought forward for at least 50 years and the Möller-Barlow disease could be seen as a medical-historical phenomenon.

Introdução: A estimativa de sobrevida de pacientes com HIV/aids aumentou após a terapia antirretroviral de alta potência: no entanto, a mortalidade por doenças hepáticas também cresceu. Objetivos: Estimar a probabilidade acumulada de sobrevida após o diagnóstico de aids entre pacientes coinfectados HIV/HCV e realizar análise exploratória para investigar fatores relacionados à sobrevida desses pacientes. Metodologia: Estudo de coorte não concorrente, utilizando sistemas de Informações: o de Agravos de Notificação, o de informação laboratorial e o de informação da vigilância epidemiológica do Centro de Referência e Treinamento DST/AIDS-SP, de pacientes com aids maiores de 13 anos, acompanhados no ambulatório geral. As variáveis estudadas foram: hepatite C, hepatite B, categoria de exposição, contagem de células T CD4+, faixa etária, escolaridade, cor, sexo e períodos de diagnóstico de aids: 1986 a 1993, 1994 a 1996, 1997 a 2002 e 2003 a 2010. Foi utilizado o estimador de Kaplan-Meier, o modelo de Cox e as estimativas das hazard ratio (HR) com os respectivos intervalos de confiança (IC 95 por cento ). Resultados: De um total de 2.864 pessoas incluídas, com idade mediana de 35 anos, 219 foram a óbito (7,5 por cento ). De 358 (12,5 por cento ) coinfectados, 159 (45,1 por cento ) eram usuários de drogas injetáveis (UDI) e de 2.506 não coinfectados, 96 (3,9 por cento ) eram UDI. A probabilidade acumulada de sobrevida entre coinfectados, a partir do diagnóstico de aids, foi 100 por cento aos 60 meses no período de 1986 a 1993; 27,8 por cento aos 168 meses no período de 1994 a 1996; 76,3 por cento aos 168 meses no período de 1997 a 2002 e 92,8 por cento aos 96 meses no período de 2003 a 2010. As curvas de sobrevida foram diferentes entre coinfectados e não coinfectados no período de 1994 a 1996 (log rank = 19,8; p < 0,001) e no período de 1997 a 2002 (log rank = 38,8; p < 0,001). No modelo de Cox multivariado, mostraram-se preditores de óbito, independentemente das outras variáveis: ter hepatite C (HR = 2,9; IC 2,1-3,9), ter hepatite B (HR = 2,5; IC 1,7-3,6), ter até 3 anos de estudo (HR = 2,3; IC 1,5-3,6), ter 50 anos ou mais de idade (HR = 2,1; IC 1,3-3,2). Ter diagnóstico de aids no período entre 1997 a 2002 mostrou-se fator de proteção ao óbito (HR = 0,4; IC 0,3-0,5). Conclusões: Coinfectados HIV/HCV apresentaram menor sobrevida quando comparado com não coinfectados nos períodos de diagnóstico de aids 1994 a 1996 e 1997 a 2002. A partir do período 1994 a 1996, observou-se aumento significativo na probabilidade acumulada de sobrevida entre coinfectados, sendo que no período 2003 a 2010, essa probabilidade foi semelhante entre coinfectados e não coinfectados, refletindo possível impacto do tratamento da hepatite C / Introduction: The estimated survival of patients with HIV/AIDS has increased after highly active antiretroviral therapy; mortality due to liver diseases, however, has also increased. Objectives: To estimate the accumulated probability of survival after AIDS diagnosis among HIV/HCV co-infected individuals and to perform an exploratory analysis to investigate factors related to the survival of these patients. Method: Non-concurrent cohort study, using data from the National Disease Reporting Information System, the laboratory and epidemiological surveillance information systems of the SP-STD Reference and Training Center-CRT, of patients over 13 years of age, followed at the general outpatient clinic. The following variables were studied: hepatitis C, hepatitis B, exposure category, T CD4+ cell count, age group, schooling, color, sex, and AIDS diagnostic periods: 1986 to 1993, 1994 to 1996, 1997 to 2002 and 2003 to 2010. Survival analysis was performed using the Kaplan-Meier estimator and the Cox model, with estimates of the hazard ratio (HR) and respective confidence intervals (95 per cent CI). Results: Of a total of 2,864 individuals included, with a median age of 35 years, 219 died (7.5 per cent ). Of the 358 (12.5 per cent ) HIV/HCV co-infected individuals, 159 (45.1 per cent ) were injecting drug users (IDU), and of the non-co-infected 2,506, 96 (3.9 per cent ) were IDU. The accumulated probability of survival among HIV/HCV co-infected individuals at 60, 168, 168 and 96 months as of AIDS diagnosis, was 100 per cent in the 1986 -1993 period; 27,8 per cent in the 1994-1996 period; 76,3 per cent in the 1997-2002 period; and 92,8 per cent in the 2003-2010 period. The survival curves were different between co-infected and non-co-infected individuals in the 1994-1996 (log rank = 19,8; p < 0,001) and in the 1997-2002 (log rank = 38,8; p < 0,001). In the multivariate model, regardless of other variables, the following were predictors of death: having hepatitis C (HR = 2.9; CI 2.1-3.9); having hepatitis B (HR = 2.5; CI 1.7-3.6); being 50 years old or over (HR = 2.1; CI 1.3-3.2) and having up to 3 years of schooling (HR = 2.3; CI 1.5-3.6). AIDS diagnosis between 1997 and 2010 was shown to be a protective factor for death (HR = 0.4; CI 0.3-0.5). Conclusions: HIV/HCV co-infected individuals had shorter survival, when compared to non-co-infected individuals in the 1994-1996 and in the 1997-2002 AIDS diagnostic periods. As of the 1994-1996 period, a significant increase in the accumulated probability of survival among HIV/HCV co-infected individuals was observed. In the 2003-2010 period, the probability was similar between co-infected and non-coinfected individuals, showing the possible impact of hepatitis treatment

Foram estudados 151 doadores de sangue encaminhados pelo Hemocentro de Ribeirão Preto ao Ambulatório de Hepatites do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto em função de terem apresentado resultados foram positivos para hepatite C nos testes de triagem pré-doação, entre 2001 e 2010. Todos tiveram confirmação diagnóstica mediante uso de técnicas de biologia molecular. No momento de chegada ao Hospital foram entrevistados por uma assistente social ligada ao Núcleo Hospitalar de Epidemiologia, com o objetivo de caracterizá-los segundo variáveis sociodemográficas, estudar fatores de risco presentes e genótipos encontrados. Houve predominância de indivíduos do sexo masculino, com baixos níveis de escolaridade e de estratos sociais menos favorecidos, com idade mediana de 36 anos. Observou-se uma tendência decrescente de infectados ao longo dos anos estudados. O genótipo mais prevalente foi o 1 com percentual de 68,8%, seguido do genótipo 3 (27,0%). Os potenciais fatores de risco mais prevalentes foram história pregressa de hospitalização sem e com cirurgia, multiplicidade de parceiros sexuais no passado, convivência com usuários de drogas, contato com sangue em atendimentos a terceiros, múltiplos parceiros sexuais no presente e contato domiciliar com casos de hepatite. Também com elevadas frequências foram observados os seguintes fatores: antecedente de transfusão sanguínea, uso coletivo de escova de dentes, história de contato sexual com usuários de drogas, frequência a creches na infância e tatuagem. Uso passado de drogas injetáveis e compartilhamento de seringas e agulhas foram relatados por 15,2% e 9,9%, respectivamente. Conclui-se que deve ter ocorrido omissão de inúmeros fatores de risco por ocasião da triagem clínica, possivelmente indicativo do desejo de se utilizar o Banco de Sangue como controle da situação sorológica por parte de parte dos doadores. / 151 blood donators were analyzed sent from the Hemocenter of Ribeirão Preto to the Hepatitis Clinic of the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, because these individuals had presented positive results for Hepatitis C in the screening tests for pre-donation, taken between 2001 and 2010. All of them had diagnosis confirmation through the use of molecular biology techniques. At the moment of arrival in the hospital, they were interviewed by a Social Assistant from the Hospital Nucleus of Epidemiology, in order to characterize them according to socio-demographic variables, to study risk factors that might be present, and genotypes found. The predominance was of male individuals, with low school levels, and coming from a less favored social stratum, with a median age of 36 years. There was a decreasing tendency of infected individuals along the years of study. The most prevailing genotype was type 1 with a percentage of 68.8%, followed by the genotype 3 (27.0%). The most prevailing potential risk factors were previous history of hospitalization with and without surgery, multiplicity of sexual partners in the past, acquaintance with drug user, contact with blood on dealing with to third parties, multiple current sexual partners and home contact with hepatitis cases. The following factors were also observed with high frequency: antecedent of blood transfusion, collective use of tooth brush, history of sexual contact with drug users, attendance to day care clinics in childhood and tattoos. Past use of injectable drugs and syringe and needle sharing were reported by 15.2% and 9.9%, respectively. The conclusion was that there must have been the omission of a number of risk factors at the time of the clinical screening, possibly indicating the desire of using the Blood Bank to make control of the serological status by some of the donators

A enzima conversora de angiotensina (ECA) catalisa a conversão de angiotensina I (Ang I) no vasoconstritor angiotensina II (Ang II) e hidrolisa a bradicinina (BK). ECA somática (sECA) possui dois domínios homólogos (N e C) que têm 60% de identidade. Embora estas duas regiões tenham homologia grande, o sítio catalítico C-domínio exibe uma atividade três vezes maior do que o N-domínio na hidrolise de Ang I in vivo. Este fato torna interessante o desenvolvimento de novos estudos de inibidores ou a melhoria dos já existentes. O objetivo deste estudo foi obter a região Ala959 até Ser1066 do Cdomínio da sECA (c-sECA), em uma estrutura conformacional semelhante à estrutura nativa. Nós amplificamos a sequência correspondente ao sítio catalítico da c-sECA com 324pb e clonamos esta sequência no vetor pET 28a(+). O segmento (nomeado de pET28_c-sECA) foi expresso em sistema bacteriano. A proteína foi expressa na forma solúvel e a purificação foi feita em uma única etapa utilizando a coluna de afinidade His-tag, a qual produziu a proteína pura. Análises estruturais por dicroísmo circular e fluorescência confirmaram que a proteína recombinante estava na conformação correta, e os ensaios de atividade mostraram que a c-sECA possui atividade enzimática e é inibida por lisinopril. / The angiotensin-converting enzyme (ACE) catalyzes the conversion of angiotensin I (Ang I) to the vasoconstrictor angiotensin II (Ang II) and the hydrolysis of bradykinin (BK). Human somatic ACE (sACE) has two homologous domains (N and C) that show 60% identity. Although these two regions have high homology, the catalytic site of the C-domain exhibits three times more activity than that of the N-domain in the hydrolysis of Ang I in vivo. This fact necessitates the development of new inhibitors or the improvement of existing ones. This study aimed to obtain the Ala959 to Ser1066 catalytic region of C-domain of sACE (c-sACE) in a structural conformation that resembles the native structure. We amplified the 324-bp sequence corresponding to the catalytic site of c-sACE and cloned this sequence into a pET28a(+) vector. The segment (named pET28_c-sACE) was expressed in a bacterial system. The expressed protein segment was soluble, and its purification was performed in one step using a His-tag affinity column. Structural analysis by circular dichroism and fluorescence confirmed that the purified protein is correctly folded, and an activity assay showed that c-sACE possesses enzymatic activity and is inhibited by lisinopril.