TY - JOUR
T1 - Design of cyclic and other templates for potent and selective peptide α-MSH analogues
AU - Fung, Selena
AU - Hruby, Victor J.
N1 - Funding Information:
The support of some of the work from our laboratory by grants from the US Public Health Service is gratefully acknowledged.
PY - 2005/8
Y1 - 2005/8
N2 - For over three decades, the design of linear peptide ligands often has incorporated cyclic constraints to improve potency, receptor selectivity, proteolytic stability and biodistribution. Its importance has been so well established that modern day schemes for ligand-based drug design often start with cyclization of linear peptides to rigidify peptide structure, to limit its conformational possibilities, and to find key pharmacophore elements in three-dimensional space. In the past several years, cyclic constraints have been used to develop ligands with improved efficacy, binding affinity, biostability and receptor selectivity for α-melanocyte-stimulating hormone (α-MSH). Furthermore, potent cyclic α-MSH analogues, such as MT-II and SHU-9119, have made structure-activity relationship studies and molecular modeling more useful for creating new three-dimensional, topographical pharmacophore templates.
AB - For over three decades, the design of linear peptide ligands often has incorporated cyclic constraints to improve potency, receptor selectivity, proteolytic stability and biodistribution. Its importance has been so well established that modern day schemes for ligand-based drug design often start with cyclization of linear peptides to rigidify peptide structure, to limit its conformational possibilities, and to find key pharmacophore elements in three-dimensional space. In the past several years, cyclic constraints have been used to develop ligands with improved efficacy, binding affinity, biostability and receptor selectivity for α-melanocyte-stimulating hormone (α-MSH). Furthermore, potent cyclic α-MSH analogues, such as MT-II and SHU-9119, have made structure-activity relationship studies and molecular modeling more useful for creating new three-dimensional, topographical pharmacophore templates.
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U2 - 10.1016/j.cbpa.2005.06.010
DO - 10.1016/j.cbpa.2005.06.010
M3 - Review article
C2 - 16023401
AN - SCOPUS:22544469452
SN - 1367-5931
VL - 9
SP - 352
EP - 358
JO - Current Opinion in Chemical Biology
JF - Current Opinion in Chemical Biology
IS - 4
ER -