Biological and conformational study of beta-substituted prolines in MT-II template: steric effects leading to human MC5 receptor selectivity.

Cai M, Cai C, Mayorov AV, Xiong C, Cabello CM, Soloshonok VA, Swift JR, Trivedi D, Hruby VJ

The journal of peptide research : official journal of the American Peptide Society1 Feb 2004Cited by 56 (Europe PMC)

PMID15009533DOI10.1111/j.1399-3011.2003.00105.xPepBankPUB-15009533

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Melanotan II.

01LabNot a test of Melanotan II aloneOther designActivity measurement
In receptor binding tests, MT-II template analogs with larger p-substituents on the phenylproline residue had 23-fold lower binding affinity at the human melanocortin-3 receptor.
In plain wordsIn lab tests, MT-II-based analogs with bulkier groups bound the human melanocortin-3 receptor 23-fold less strongly.
Peptide
Melanotan II
Outcome
DecreaseBinding affinity at hMC3R of 3-(p-methoxyphenyl)-Pro6 analog versus 3-phenyl-Pro6 analog
Study
humann: not reported in source
Human melanocortin receptors (hMC3R, hMC4R, hMC5R)
Outcome group
Receptor activity and mechanism · Pharmacology
Measurements
Binding affinity decrease
23-fold
hMC3R
Source sentences
Summary
From (2S, 3R)-3-phenyl-Pro6 to (2S, 3R)-3-(p-methoxyphenyl)-Pro6 analogs the binding affinity decreased 23-fold at the human melanocortin-3 receptor (hMC3R), 17-fold at the hMC4R, and eight-fold at the hMC5R, but selectivity for the hMC5R increased.
1 context sentence(design, population, supporting numbers)
Summary · context
To investigate the molecular basis for the interaction of the chi-constrained conformation of melanotropin peptide with the human melanocortin receptors, a series of beta-substituted proline analogs were synthesized and incorporated into the Ac-Nle-C[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (MT-II) template a…
In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.
Report a problemFND-1500953301
02LabNot a test of Melanotan II aloneOther designActivity measurement
In receptor binding tests, MT-II template analogs with larger p-substituents on the phenylproline residue had 17-fold lower binding affinity at the human melanocortin-4 receptor.
In plain wordsIn lab tests, MT-II-based analogs with bulkier groups bound the human melanocortin-4 receptor 17-fold less strongly.
Peptide
Melanotan II
Outcome
DecreaseBinding affinity at hMC4R of 3-(p-methoxyphenyl)-Pro6 analog versus 3-phenyl-Pro6 analog
Study
humann: not reported in source
Human melanocortin receptors (hMC3R, hMC4R, hMC5R)
Outcome group
Receptor activity and mechanism · Pharmacology
Measurements
Binding affinity decrease
17-fold
hMC4R
Source sentences
Summary
From (2S, 3R)-3-phenyl-Pro6 to (2S, 3R)-3-(p-methoxyphenyl)-Pro6 analogs the binding affinity decreased 23-fold at the human melanocortin-3 receptor (hMC3R), 17-fold at the hMC4R, and eight-fold at the hMC5R, but selectivity for the hMC5R increased.
1 context sentence(design, population, supporting numbers)
Summary · context
To investigate the molecular basis for the interaction of the chi-constrained conformation of melanotropin peptide with the human melanocortin receptors, a series of beta-substituted proline analogs were synthesized and incorporated into the Ac-Nle-C[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (MT-II) template a…
In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.
Report a problemFND-1500953302
03LabNot a test of Melanotan II aloneOther designActivity measurement
In receptor binding tests, MT-II template analogs with larger p-substituents on the phenylproline residue had eight-fold lower binding affinity at the human melanocortin-5 receptor.
In plain wordsIn lab tests, MT-II-based analogs with bulkier groups bound the human melanocortin-5 receptor eight-fold less strongly.
Peptide
Melanotan II
Outcome
DecreaseBinding affinity at hMC5R of 3-(p-methoxyphenyl)-Pro6 analog versus 3-phenyl-Pro6 analog
Study
humann: not reported in source
Human melanocortin receptors (hMC3R, hMC4R, hMC5R)
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
From (2S, 3R)-3-phenyl-Pro6 to (2S, 3R)-3-(p-methoxyphenyl)-Pro6 analogs the binding affinity decreased 23-fold at the human melanocortin-3 receptor (hMC3R), 17-fold at the hMC4R, and eight-fold at the hMC5R, but selectivity for the hMC5R increased.
1 context sentence(design, population, supporting numbers)
Summary · context
To investigate the molecular basis for the interaction of the chi-constrained conformation of melanotropin peptide with the human melanocortin receptors, a series of beta-substituted proline analogs were synthesized and incorporated into the Ac-Nle-C[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (MT-II) template a…
In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.
Report a problemFND-1500953303
04LabNot a test of Melanotan II aloneOther designActivity measurement
In receptor binding tests, selectivity of the MT-II template analogs for the human melanocortin-5 receptor increased as p-substituent size increased.
In plain wordsIn lab tests, MT-II-based analogs with bulkier groups became more selective for the human melanocortin-5 receptor.
Peptide
Melanotan II
Outcome
IncreaseSelectivity for hMC5R
Study
humann: not reported in source
Human melanocortin receptors (hMC3R, hMC4R, hMC5R)
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
From (2S, 3R)-3-phenyl-Pro6 to (2S, 3R)-3-(p-methoxyphenyl)-Pro6 analogs the binding affinity decreased 23-fold at the human melanocortin-3 receptor (hMC3R), 17-fold at the hMC4R, and eight-fold at the hMC5R, but selectivity for the hMC5R increased.
1 context sentence(design, population, supporting numbers)
Summary · context
To investigate the molecular basis for the interaction of the chi-constrained conformation of melanotropin peptide with the human melanocortin receptors, a series of beta-substituted proline analogs were synthesized and incorporated into the Ac-Nle-C[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (MT-II) template a…
In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.
Report a problemFND-1500953304
05LabNot a test of Melanotan II aloneOther designActivity measurement
In receptor binding tests, replacing D-Phe7 in the MT-II template with (2R, 3S)-3-phenyl-Pro greatly reduced binding affinity at these melanocortin receptors.
In plain wordsIn lab tests, replacing one amino acid in the MT-II template greatly reduced binding to melanocortin receptors.
Peptide
Melanotan II
Outcome
DecreaseBinding affinity of D-Phe7 to 3-phenyl-Pro substituted analog
Study
humann: not reported in source
Human melanocortin receptors (hMC3R, hMC4R, hMC5R)
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
In addition, the substitution of the D-Phe7 residue with a (2R, 3S)-3-phenyl-Pro resulted in greatly reduced binding affinity (10(3)-10(5)) at these melanocortin receptors.
1 context sentence(design, population, supporting numbers)
Summary · context
To investigate the molecular basis for the interaction of the chi-constrained conformation of melanotropin peptide with the human melanocortin receptors, a series of beta-substituted proline analogs were synthesized and incorporated into the Ac-Nle-C[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (MT-II) template a…
In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.
Report a problemFND-1500953305
06Computer modelNot a test of Melanotan II aloneIn silicoOther
In force-field simulations, MT-II and SHU-9119 shared a similar backbone conformation and topography, except for the orientation of the D-Phe7 or D-Nal (2')7 side chain.
In plain wordsIn computer simulations, MT-II and SHU-9119 had a similar backbone shape, differing in one side chain.
Peptide
Melanotan II
Outcome
Not applicableBackbone conformation of MT-II versus SHU-9119
Study
n: not reported in source
Macromodel LLMOD with OPLS-AA force field simulation
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
Macromodel's Large Scale Low Mode (LLMOD) with OPLS-AA force field simulations revealed that both MT-II and SHU-9119 share a similar backbone conformation and topography with the exception of the orientation of the side chains of D-Phe7/D-Nal (2')7 in chi space.
1 context sentence(design, population, supporting numbers)
Summary · context
To investigate the molecular basis for the interaction of the chi-constrained conformation of melanotropin peptide with the human melanocortin receptors, a series of beta-substituted proline analogs were synthesized and incorporated into the Ac-Nle-C[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (MT-II) template a…
In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.
Report a problemFND-1500953306

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 09:43 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

PepBank is a research reference. Talk to a doctor before you use any peptide.