Navegando por Palavras-chave "disulfide bridge"

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    Highly Potential Antiplasmodial Restricted Peptides
    (Wiley-Blackwell, 2015-02-01) Der Torossian, Torres Marcelo; Silva, Adriana F.; Alves, Flavio L. [UNIFESP]; Capurro, Margareth L.; Miranda, Antonio [UNIFESP]; Xavier, Oliveira Vani; Universidade Federal do ABC (UFABC); Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Malaria is an infectious disease responsible for approximately one million deaths annually. the antimalarial effects of angiotensin II and its analogs against Plasmodium gallinaceum and P.falciparum have recently been reported. To evaluate antiplasmodial activity, we synthesized five angiotensin II-restricted analogs containing disulfide bridges. To accomplish this, peptides containing two inserted amino acid residues (cysteine) were synthesized by the Fmoc solid-phase method, purified by liquid chromatography, and characterized by mass spectrometry. Conformational studies were performed by circular dichroism. the results indicated that two of the analogs had higher antiplasmodium activity (92% and 98% activity) than angiotensin II (88% activity), measured by fluorescence microscopy. Results showed that the insertion position must be selected, to preserve the hydrophobic interactions between the non-polar residues, as this affects antiplasmodial activity. the circular dichroism studies suggested that the active analogs as well as the native angiotensin II adopt a -turn conformation in different solutions. This approach provided insight for understanding the effects of restricting the ring size and position on the bioactivity of angiotensin II and provides a new direction for the design of potential chemotherapeutic agents.
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    Structure-activity relationship studies of gomesin: Importance of the disulfide bridges for conformation, bioactivities, and serum stability
    (Wiley-Blackwell, 2006-01-01) Fazio, M. A.; Oliveira, V. X.; Bulet, P.; Miranda, MTM; Daffre, S.; Miranda, A.; Universidade Federal de São Paulo (UNIFESP); Bernex; Universidade de São Paulo (USP)
    Gomesin is an antimicrobial peptide isolated from hemocytes of the Brazilian spider Acanthoscurria gomesiana that contains two disulfide bridges Cys(2-15)/Cys(6-11) and presents a beta-hairpin structure. To investigate the role of the disulfide bridges on gomesin conformation, bioactivities, and serum stability, structure-activity relationship (SAR) studies were conducted. Initially, gomesin and variants lacking one or both disulfide bridges were synthesized. CD studies showed that the gomesin structure is very rigid independently of the solvent enviromnent. On the other hand, the linearized analogues adopted secondary structures according to the environment, while the monocyclic disulfide-bridged peptides had a tendency to adopt a turn structure. the absence of one or both bridges resulted in a decrease in the antimicrobial and hemolytic activities. in addition, serum stability studies revealed that, contrasting to gomesin that was stable even after 48 h of incubation, the linearized analogues were rapidly degraded. the replacement of the disulfide bounds by lactam bridges led to monocyclic and bicyclic compounds. SAR studies indicated that the monocyclic lactam-bridged analogues tend to assume a alpha-helical structure being less potent, hemolytic, and serum stable than the wild-type gomesin. On the other hand, the bicyclic lactam/disulfide-bridged analogues displayed a similar conformation and degradation kinetics identical to gomesin. However, the antimicrobial activity appeared to be dependent on the lactam bridge position and size. These findings indicated that (i) the secondary structure plays a pivotal role for the full activity of gomesin; (ii) the antimicrobial and hemolytic activities of gomesin are correlated events; (iii) while at least one of the disulfide bridges is needed for the maintenance of a significant antimicrobial activity of gomesin, both bridges are required for high serum stability and optimal conformation; and finally (iv) the best analogue obtained was the bicyclo (2-15,6-11)[Glu(2), Cys(6.11), Lys(15) J-Gm since it is as stable and potent as gomesin. (c) 2005 Wiley Periodicals, Inc.