TY - JOUR
T1 - Design of peptide and peptidomimetic ligands with novel pharmacological activity profiles
AU - Hruby, Victor J.
AU - Cai, Minying
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/1
Y1 - 2013/1
N2 - Peptide hormones and neurotransmitters are of central importance in most aspects of intercellular communication and are involved in virtually all degenerative diseases. In this review, we discuss physicochemical approaches to the design of novel peptide and peptidomimetic agonists, antagonists, inverse agonists, and related compounds that have unique biological activity profiles, reduced toxic side effects, and, if desired, the ability to cross the blood-brain barrier. Designing ligands for specific biological and medical needs is emphasized, as is the close collaboration of chemists and biologists to maximize the chances for success. Special emphasis is placed on the use of conformational (φ-ψ space) and topographical (χ space) considerations in design.
AB - Peptide hormones and neurotransmitters are of central importance in most aspects of intercellular communication and are involved in virtually all degenerative diseases. In this review, we discuss physicochemical approaches to the design of novel peptide and peptidomimetic agonists, antagonists, inverse agonists, and related compounds that have unique biological activity profiles, reduced toxic side effects, and, if desired, the ability to cross the blood-brain barrier. Designing ligands for specific biological and medical needs is emphasized, as is the close collaboration of chemists and biologists to maximize the chances for success. Special emphasis is placed on the use of conformational (φ-ψ space) and topographical (χ space) considerations in design.
KW - blood-brain barrier
KW - conformation and biological activity
KW - peptide hormones
KW - peptide neurotransmitters
KW - peptide pharmacophores
KW - peptide stability
KW - topographical structures
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U2 - 10.1146/annurev-pharmtox-010510-100456
DO - 10.1146/annurev-pharmtox-010510-100456
M3 - Review article
C2 - 23294313
AN - SCOPUS:84872260755
VL - 53
SP - 557
EP - 580
JO - Annual Review of Pharmacology and Toxicology
JF - Annual Review of Pharmacology and Toxicology
SN - 0362-1642
ER -