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Proposed Bioactive Conformations of Opiorphin, an Endogenous Dual APN/NEP Inhibitor.

ABSTRACT: The conformational profiles for the endogenous peptide Opiorphin and a set of seven analogues exhibiting different inhibitory activities toward human aminopeptidase N (hAPN) and human neprilysin (hNEP) were independently computed to deduce a bioactive conformation that Opiorphin may adopt when binding these two enzymes. The conformational space was thoroughly sampled using an iterative simulated annealing protocol, and a library of low-energy conformers was generated for each peptide. Bioactive Opiorphin conformations fitting our experimental structure-activity relationship data were identified for hAPN and hNEP using computational pairwise comparisons between each of the unique low-energy conformations of Opiorphin and its analogues. The obtained results provide a structural explanation for the dual hAPN and hNEP inhibitory activity of Opiorphin and show that the inborn flexibility of Opiorphin is essential for its analgesic activity.

SUBMITTER: Pinto M

PROVIDER: S-EPMC4025773 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Proposed Bioactive Conformations of Opiorphin, an Endogenous Dual APN/NEP Inhibitor.

Pinto Marta M Rougeot Catherine C Gracia Luis L Rosa Mònica M García Andrés A Arsequell Gemma G Valencia Gregorio G Centeno Nuria B NB

ACS medicinal chemistry letters 20111117 1

The conformational profiles for the endogenous peptide Opiorphin and a set of seven analogues exhibiting different inhibitory activities toward human aminopeptidase N (hAPN) and human neprilysin (hNEP) were independently computed to deduce a bioactive conformation that Opiorphin may adopt when binding these two enzymes. The conformational space was thoroughly sampled using an iterative simulated annealing protocol, and a library of low-energy conformers was generated for each peptide. Bioactive ...[more]

PMID: 24900367

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Proposed Bioactive Conformations of Opiorphin, an Endogenous Dual APN/NEP Inhibitor.

Publications

Proposed Bioactive Conformations of Opiorphin, an Endogenous Dual APN/NEP Inhibitor.

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