NMR Studies on Turn Mimetic Analogs Derived from Melanocyte-stimulating Hormones

Cho, Min Kyu; Kim, Sung Soo; Lee, Myung Ryul; Shin, Jongmoon; Lee, Jiyong; Lim, Sung Kil; Baik, Ja Hyun; Yoon, Chang-Ju; Shin, Injae; Lee, Weontae

doi:10.5483/bmbrep.2003.36.6.552

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…Cross‐peaks which were overlapped more than 50% were treated as weak restraints in the dyana calculation. For each examined peptide, an ensemble of 200 structures was generated with the simulated annealing standard protocol of the program dyana (45–50). Fifty structures were chosen, whose interprotonic distances best fitted NOE‐derived distances, and then refined through successive steps of restrained and unrestrained EM calculations.…”

Section: Methodsmentioning

confidence: 99%

“…Conformational analysis of a-MSH(6-13) (1) Conformational preferences of the parent peptide 1 were investigated taking also in consideration the previous NMR studies performed on whole sequence of a-MSH (45)(46)(47)(48)(49)(50). A series of medium range NOE contacts were observable in the NOESY spectrum along the entire sequence of the peptide (H a -NH i+2 connectivities between Phe 7 -Trp 9 , Arg 8 -Gly 10 , Trp 9 -Lys 11 and Lys 11 -Val 13 ) suggested the presence of several consecutive b-turn structures.…”

Section: Nmr Analysismentioning

confidence: 99%

“…The NOE-based distance restraints were obtained from NOESY spectra collected with a mixing time of 200 mseconds. The NOE cross-peaks were integrated with the XEASY program and were converted into upper distance bounds using the CALIBA program incorporated into the program package DYANA (45)(46)(47)(48)(49)(50). Cross-peaks which were overlapped more than 50% were treated as weak restraints in the DYANA calculation.…”

Section: Structural Determinations and Computational Modellingmentioning

confidence: 99%

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Structure–function Relationships and Conformational Properties of α‐MSH(6–13) Analogues with Candidacidal Activity

et al. 2007

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Alpha-melanocyte-stimulating hormone (alpha-MSH) is an endogenous linear tridecapeptide with potent anti-inflammatory effects. We firstly demonstrated that alpha-MSH and its C-terminal sequence Lys-Pro-Val [alpha-MSH(11-13)] have antimicrobial effects against two major and representative pathogens: Staphylococcus aureus and Candida albicans. Successively, in an attempt to improve the candidacidal activity of alpha-MSH and to better understand the peptide structure-antifungal activity relations, we have recently designed and synthesized novel peptide analogues. We focused on the sequence alpha-MSH(6-13), which contains the invariant melanocortin core sequence His-Phe-Arg-Trp (6-9) and also contains the sequence Lys-Pro-Val (11-13) important for antimicrobial activity. In that structure-activity study, we discovered several compounds that have greater candidacidal activity than alpha-MSH, among which the peptide [d-Nal-7,Phe-12]-alpha-MSH(6-13) was the most potent. Here, we report a detailed conformational analysis by spectroscopic and computational methods of three peptides, alpha-MSH(6-13) (1), [d-Nal-7,Phe-12]-alpha-MSH(6-13) (2) and [d-Nal-7,Asp-12]-alpha-MSH(6-13) (3). Peptides were chosen on the basis of their candidacidal activities and were studied in membrane mimetic environment (SDS micelles). Different turn structures were observed for the three peptides and a conformation-activity model was developed based on these results. This study offers a structural basis for the design of novel peptide and non-peptide analogues to be used as new antimicrobial agents.

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Section: Methodsmentioning

confidence: 99%

Section: Nmr Analysismentioning

confidence: 99%

Section: Structural Determinations and Computational Modellingmentioning

confidence: 99%

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Structure–function Relationships and Conformational Properties of α‐MSH(6–13) Analogues with Candidacidal Activity

et al. 2007

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“…dihedral angles, and 8 hydrogen-bond restraints were used. Crosspeak volumes were classified as strong, medium, or weak, corresponding to upper bound interproton distance restraints of 2.7, 3.3 and 5.0 Å, respectively (Cho et al, 2003). Backbone dihedral restraints inferred from 3 J HNα coupling constants were used as −55 ± 5 o for a 3 J HNa of less than 6 Hz (Wagner et al, 1987;.…”

Section: Structural Restraints and Structure Calculationsmentioning

confidence: 99%

Solution Structure of Human Orexin-A: Regulator of Appetite and Wakefulness

Kim

Hong

Kim³

et al. 2004

BMB Reports

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Orexin-A and orexin-B (hypocretin-1 and hypocretin-2, respectively) are important hypothalamic neuro-peptides, which are encoded by a single mRNA transcript and stimulate food intake as well as regulate wakefulness. Here we determined the solution structure of orexin-A by NMR spectroscopy and by simulated-annealing calculation. The structural features of orexin-A involve two alpha-helices, with the hydrophobic residues disposed to on one side of helix, and hydrophilic residues to the other. A hydrophilic turn induced by two disulfide bonds provides the key difference between orexin-A and -B. With previous mutagenic studies, the derived structure of orexin-A provides us with a structure-functional view for novel drug design.

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Fixierung cyclischer Peptide: Mimetika von Proteinstrukturmotiven

et al. 2014

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Viele Proteine entfalten ihre biologische Aktivität über kleine exponierte Oberflächenregionen aus gefalteten Peptiden mit wohldefinierten dreidimensionalen Strukturen, Epitope genannt. Kurze synthetische Peptidsequenzen, die diesen bioaktiven Proteinoberflächen entsprechen, bilden in Wasser keine thermodynamisch stabilen proteinähnlichen Strukturen. Die Bildung proteinähnlicher biologisch aktiver Konformationen (Stränge, Helices, Kehren) kann jedoch durch Cyclisierung in Verbindung mit anderen molekularen Verstrebungen induziert werden. Letztere helfen bei der Feinabstimmung der dreidimensionalen Struktur. Solche fixierten cyclischen Peptide können ähnliche biologische Aktivitäten und Wirkungen wie das als Vorbild dienende Protein haben, sodass sie als biologische Sonden und Leitstrukturen für Therapeutika, Diagnostika und Impfstoffe dienen können. Dieser Aufsatz beleuchtet Beispiele für cyclische Peptide, die dreidimensionale Strukturen von Strang‐, Kehren‐ oder Helixabschnitten von Peptiden und Proteinen nachahmen und beschreibt einige weitere Elemente, die in cyclisch peptidischen Naturstoffen und synthetischen makrocyclischen Peptidomimetika vorkommen, dort die Peptidstruktur verfeinern und ihr biologische Aktivitäten verleihen.

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NMR Studies on Turn Mimetic Analogs Derived from Melanocyte-stimulating Hormones

Cited by 4 publications

References 24 publications

Structure–function Relationships and Conformational Properties of α‐MSH(6–13) Analogues with Candidacidal Activity

Structure–function Relationships and Conformational Properties of α‐MSH(6–13) Analogues with Candidacidal Activity

Solution Structure of Human Orexin-A: Regulator of Appetite and Wakefulness

Fixierung cyclischer Peptide: Mimetika von Proteinstrukturmotiven

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