Fine-tuning the n-n; aromatic interactions in peptides: somatostatin analogues containing mesityl alanine.

PABLO MARTÍN-GAGO; MARC GOMEZ-CAMILAS; ROSARIO RAMÓN; XAVIER VERDAGUER; PAU MARTIN-MALPARTIDA; ERIC ARAGON; JIMENA FERNANDEZ-CARNEADO; BERTA PONSATI; PILAR LÓPEZ-RUIZ; M. ALICIA CORTÉS; BEGOÑA COLÁS; MARIA J. MACIAS; ANTONI RIERA

ANGEWANDTE CHEMIE

VCH PUBLISHERS INC

Lugar: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim; Año: 2012 vol. 51 p. 1820 - 1825

0570-0833

Factor de impacto: 13,455/ Journal Ranking: Q1. Understanding noncovalent interactions between aromaticmoieties is essential in medicinal chemistry and lead optimizationfor drug design. These interactions are fundamentalin controlling diverse phenomena; for example, verticalstacking interactions provide stability to duplex DNA.[1]Other important examples include the spike nucleocapsidinteraction in viruses,[2a] molecular self-assembly in supramolecularsystems,[2b] and host?guest molecular recognitionevents.[2c] Aromatic amino acids strongly contribute to proteinarchitecture and stability[3,4] as it has been observed in SH3and WW domains,[5a] and of peptides, including the antimicrobialTachiplesin I[5b] or the pharmacologically importanthormone somatostatin.[6]Somatostatin, also known as somatotropin release-inhibitingfactor (SRIF), is a 14-amino-acid natural peptide whosesequence is shown in Figure 1 (left). In clinical practice,somatostatin is currently used as a gastric anti-secretory drugto treat growth hormone secretion disorders and endocrinetumors.[7] It is involved in multiple biological functionsmediated by direct interactions between it and at least fivecharacterized G-protein-coupled receptors, named SSTR15.[8] These receptors differ in their tissue distribution andpharmacological properties.