Synthesis and evaluation of new endomorphin analogues modified at the Pro2 residue

Domenica Torino; Adriano Mollica; Francesco Pinnen; Gino Lucente; Federica Feliciani; Peg Davis; Josephine Lai; Shou Wu Ma; Frank Porreca; Victor J. Hruby

doi:10.1016/j.bmcl.2009.06.008

Synthesis and evaluation of new endomorphin analogues modified at the Pro² residue

Domenica Torino
, Adriano Mollica
, Francesco Pinnen
, Gino Lucente
, Federica Feliciani
, Peg Davis
, Josephine Lai
, Shou Wu Ma
, Frank Porreca
, Victor J. Hruby

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Six new endomorphin analogues, incorporating constrained amino acids in place of native proline have been synthesized. Residues of (S)-azetidine-2-carboxylic acid (Aze), 3,4-dehydro-(S)-proline (Δ³Pro), azetidine-3-carboxylic acid (3Aze) and dehydro-alanine (ΔAla) have been used to prepare [Δ³Pro²]EM-2 (1), [Aze²]EM-1 (2), [Aze²]EM-2 (3), [3Aze²]EM-1 (4), [3Aze²]EM-2 (5) and [ΔAla²]EM-2 (6). Binding assays and functional bioactivities for μ- and δ-receptors are reported. The highest affinity, bioactivity and selectivity are shown by peptides 2 and 3 containing the Aze residue.

Original language	English (US)
Pages (from-to)	4115-4118
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2009.06.008
State	Published - Aug 1 2009

Keywords

3,4-Didehydro-(S)-proline
Azetidine carboxylic acids
Didehydro-alanine
Endomorphins
μ-Receptors

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2009.06.008

Cite this

@article{a31f3515b4d340a59a58e945c2df2898,

title = "Synthesis and evaluation of new endomorphin analogues modified at the Pro2 residue",

abstract = "Six new endomorphin analogues, incorporating constrained amino acids in place of native proline have been synthesized. Residues of (S)-azetidine-2-carboxylic acid (Aze), 3,4-dehydro-(S)-proline (Δ3Pro), azetidine-3-carboxylic acid (3Aze) and dehydro-alanine (ΔAla) have been used to prepare [Δ3Pro2]EM-2 (1), [Aze2]EM-1 (2), [Aze2]EM-2 (3), [3Aze2]EM-1 (4), [3Aze2]EM-2 (5) and [ΔAla2]EM-2 (6). Binding assays and functional bioactivities for μ- and δ-receptors are reported. The highest affinity, bioactivity and selectivity are shown by peptides 2 and 3 containing the Aze residue.",

keywords = "3,4-Didehydro-(S)-proline, Azetidine carboxylic acids, Didehydro-alanine, Endomorphins, μ-Receptors",

author = "Domenica Torino and Adriano Mollica and Francesco Pinnen and Gino Lucente and Federica Feliciani and Peg Davis and Josephine Lai and Ma, \{Shou Wu\} and Frank Porreca and Hruby, \{Victor J.\}",

note = "Funding Information: This research was supported in part by grants from the U.S. Public Health Service, National Institute of Drug Abuse DA06284 and DA13449 (V.J.H.).",

year = "2009",

month = aug,

day = "1",

doi = "10.1016/j.bmcl.2009.06.008",

language = "English (US)",

volume = "19",

pages = "4115--4118",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

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TY - JOUR

T1 - Synthesis and evaluation of new endomorphin analogues modified at the Pro2 residue

AU - Torino, Domenica

AU - Mollica, Adriano

AU - Pinnen, Francesco

AU - Lucente, Gino

AU - Feliciani, Federica

AU - Davis, Peg

AU - Lai, Josephine

AU - Ma, Shou Wu

AU - Porreca, Frank

AU - Hruby, Victor J.

N1 - Funding Information: This research was supported in part by grants from the U.S. Public Health Service, National Institute of Drug Abuse DA06284 and DA13449 (V.J.H.).

PY - 2009/8/1

Y1 - 2009/8/1

N2 - Six new endomorphin analogues, incorporating constrained amino acids in place of native proline have been synthesized. Residues of (S)-azetidine-2-carboxylic acid (Aze), 3,4-dehydro-(S)-proline (Δ3Pro), azetidine-3-carboxylic acid (3Aze) and dehydro-alanine (ΔAla) have been used to prepare [Δ3Pro2]EM-2 (1), [Aze2]EM-1 (2), [Aze2]EM-2 (3), [3Aze2]EM-1 (4), [3Aze2]EM-2 (5) and [ΔAla2]EM-2 (6). Binding assays and functional bioactivities for μ- and δ-receptors are reported. The highest affinity, bioactivity and selectivity are shown by peptides 2 and 3 containing the Aze residue.

AB - Six new endomorphin analogues, incorporating constrained amino acids in place of native proline have been synthesized. Residues of (S)-azetidine-2-carboxylic acid (Aze), 3,4-dehydro-(S)-proline (Δ3Pro), azetidine-3-carboxylic acid (3Aze) and dehydro-alanine (ΔAla) have been used to prepare [Δ3Pro2]EM-2 (1), [Aze2]EM-1 (2), [Aze2]EM-2 (3), [3Aze2]EM-1 (4), [3Aze2]EM-2 (5) and [ΔAla2]EM-2 (6). Binding assays and functional bioactivities for μ- and δ-receptors are reported. The highest affinity, bioactivity and selectivity are shown by peptides 2 and 3 containing the Aze residue.

KW - 3,4-Didehydro-(S)-proline

KW - Azetidine carboxylic acids

KW - Didehydro-alanine

KW - Endomorphins

KW - μ-Receptors

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