NMR and quenched molecular dynamics studies of superpotent linear and cyclic α-melanotropins

Fahad Al-Obeidi; Steven D. O'Connor; Constantin Job; Victor J. Hruby; B. Montgomery Pettitt

doi:10.1111/j.1399-3011.1998.tb00640.x

NMR and quenched molecular dynamics studies of superpotent linear and cyclic α-melanotropins

Fahad Al-Obeidi, Steven D. O'Connor, Constantin Job, Victor J. Hruby, B. Montgomery Pettitt

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

37 Scopus citations

Abstract

Conformational searching, computer simulations, synthesis and NMR are used on a variety of α melanocyte-stimulating hormone (α-MSH) analogues to understand the physical characteristics required for biological potency. Peptides I (Ac-[Nle⁴,Asp⁵,D-Phe⁷,Lys¹⁰]α-MSH(4-10)-NH₂), II (Ac- c[Nle⁴,Asp⁵,D-Phe⁷,Lys¹⁰]α-MSH(4-10)-NH₂) and III (Ac-[Nle⁴,Asp⁵,D- Phe⁷,Dap¹⁰]α-MSH(4-10)-NH₂ all show very similar conformational properties (backbone and side-chain torsional angles), and all-display high biological potencies. The modeling results for these compounds are supported by the NMR data. Peptide IV (Ac-c[Nle⁴,Asp⁵,D-Phe⁷,Dap¹⁰]α-MSH(4-10)- NH₂) appears to have a markedly different conformation and has decreased biological potency.

Original language	English (US)
Pages (from-to)	420-431
Number of pages	12
Journal	Journal of Peptide Research
Volume	51
Issue number	6
DOIs	https://doi.org/10.1111/j.1399-3011.1998.tb00640.x
State	Published - 1998
Externally published	Yes

Keywords

Cyclic melanotropins
NMR
Quenched molecular dynamics
α-melanotropin

ASJC Scopus subject areas

Biochemistry
Endocrinology

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10.1111/j.1399-3011.1998.tb00640.x

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title = "NMR and quenched molecular dynamics studies of superpotent linear and cyclic α-melanotropins",

abstract = "Conformational searching, computer simulations, synthesis and NMR are used on a variety of α melanocyte-stimulating hormone (α-MSH) analogues to understand the physical characteristics required for biological potency. Peptides I (Ac-[Nle4,Asp5,D-Phe7,Lys10]α-MSH(4-10)-NH2), II (Ac- c[Nle4,Asp5,D-Phe7,Lys10]α-MSH(4-10)-NH2) and III (Ac-[Nle4,Asp5,D- Phe7,Dap10]α-MSH(4-10)-NH2 all show very similar conformational properties (backbone and side-chain torsional angles), and all-display high biological potencies. The modeling results for these compounds are supported by the NMR data. Peptide IV (Ac-c[Nle4,Asp5,D-Phe7,Dap10]α-MSH(4-10)- NH2) appears to have a markedly different conformation and has decreased biological potency.",

keywords = "Cyclic melanotropins, NMR, Quenched molecular dynamics, α-melanotropin",

author = "Fahad Al-Obeidi and O'Connor, {Steven D.} and Constantin Job and Hruby, {Victor J.} and Pettitt, {B. Montgomery}",

year = "1998",

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AU - Al-Obeidi, Fahad

AU - O'Connor, Steven D.

AU - Job, Constantin

AU - Hruby, Victor J.

AU - Pettitt, B. Montgomery

PY - 1998

Y1 - 1998

N2 - Conformational searching, computer simulations, synthesis and NMR are used on a variety of α melanocyte-stimulating hormone (α-MSH) analogues to understand the physical characteristics required for biological potency. Peptides I (Ac-[Nle4,Asp5,D-Phe7,Lys10]α-MSH(4-10)-NH2), II (Ac- c[Nle4,Asp5,D-Phe7,Lys10]α-MSH(4-10)-NH2) and III (Ac-[Nle4,Asp5,D- Phe7,Dap10]α-MSH(4-10)-NH2 all show very similar conformational properties (backbone and side-chain torsional angles), and all-display high biological potencies. The modeling results for these compounds are supported by the NMR data. Peptide IV (Ac-c[Nle4,Asp5,D-Phe7,Dap10]α-MSH(4-10)- NH2) appears to have a markedly different conformation and has decreased biological potency.

AB - Conformational searching, computer simulations, synthesis and NMR are used on a variety of α melanocyte-stimulating hormone (α-MSH) analogues to understand the physical characteristics required for biological potency. Peptides I (Ac-[Nle4,Asp5,D-Phe7,Lys10]α-MSH(4-10)-NH2), II (Ac- c[Nle4,Asp5,D-Phe7,Lys10]α-MSH(4-10)-NH2) and III (Ac-[Nle4,Asp5,D- Phe7,Dap10]α-MSH(4-10)-NH2 all show very similar conformational properties (backbone and side-chain torsional angles), and all-display high biological potencies. The modeling results for these compounds are supported by the NMR data. Peptide IV (Ac-c[Nle4,Asp5,D-Phe7,Dap10]α-MSH(4-10)- NH2) appears to have a markedly different conformation and has decreased biological potency.

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KW - NMR

KW - Quenched molecular dynamics

KW - α-melanotropin

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NMR and quenched molecular dynamics studies of superpotent linear and cyclic α-melanotropins

Abstract

Keywords

ASJC Scopus subject areas

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