Strategies for cyclizations of novel peptides on solid supports

Hruby, Victor J.; Wilke, Susanne; Al‐Obeidi, Fahad; Ding, Jiao; Lin, Ying

doi:10.1016/0923-1137(94)90121-x

Cited by 11 publications

(13 citation statements)

References 25 publications

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“…Cyclization on the resin was performed following the method of Hruby et al . (56). An hydrogen fluoride (HF) reaction was used to cleavage the peptide from the resin and the side chain protecting groups.…”

Section: Peptide Synthesismentioning

confidence: 99%

Biological and conformational study of β‐substituted prolines in MT‐II template: steric effects leading to human MC5 receptor selectivity*

Cai

Mayorov

et al. 2004

The Journal of Peptide Research

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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 at the His6 and D-Phe7 positions. It was found that the binding affinities generally diminished as the steric bulk of the p-substituents of the 3-phenylproline residues increased. 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. 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. 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. Introduction of the dihedrally constrained phenylproline analogs into the His6 position (analogs 2-6) caused topographical changes that might be responsible for the lower binding affinities. Our findings indicate that hMC3 and hMC4 receptors are more sensitive to steric effects and conformational constraints than the hMC5 receptor. This is the first example for melanocortin receptor selectivity where the propensity of steric interactions in chi space of beta-modified Pro6 analogs of MT-II has been shown to play a critical role for binding as well as bioefficacy of melanotropins at hMC3 and hMC4 receptors, but not at the hMC5 receptor.

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Section: Peptide Synthesismentioning

confidence: 99%

Biological and conformational study of β‐substituted prolines in MT‐II template: steric effects leading to human MC5 receptor selectivity*

Cai

Mayorov

et al. 2004

The Journal of Peptide Research

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“…Both the on-resin lactamization and the disulfide formation in solution were observed to be sequence-dependent. In A similar Boc/Bn/Fm strategy has been applied to the synthesis of bicyclic analogs of endothelin [51], oxytocin [52] and fasciculin loop II [53]. After the peptide chain assembly, the Fmoc and/or Fm groups were removed with piperidine and the lactam bridge was formed on the support.…”

Section: Scheme 12mentioning

confidence: 99%

Synthesis of Bicyclic Peptides

Karskela¹,

Virta²,

Lönnberg

2006

COS

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“…This can be achieved, for example, by the site of attachment on the target molecule being transformed into a C-H bond, 4,[7][8][9][10][11][12][13] or by a combined cyclization-cleavage reaction. 4,[14][15][16][17][18][19] Small molecules or oligomers with conjugated π-electron systems are of interest because of their potential applications in molecular electronics. [7][8][9]10,13,[20][21][22][23][24][25][26][27][28][29][30] They can also serve as valuable models for the corresponding polymers.…”

Section: Introductionmentioning

confidence: 99%

Polymer-supported syntheses of thiophene-containing compounds using a new type of traceless linker

Ben-Haida

Hodge

2012

Org. Biomol. Chem.

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A new type of traceless linker is described for use in polymer-supported (PS) syntheses of thiophene-containing compounds. It is based on the cleavage of PS aryl 2-thienyl ketones by a mixture of potassium t-butoxide and water (typical mol ratio 10:3) in an ethereal solvent. Cleavage occurs to give the soluble thiophene-containing product. The method is used to prepare a range of eight thiophene-containing compounds including a terthiophene and a dialkylquaterthiophene. PS unsymmetrical diaryl ketones incorporating, for example, ortho-methoxyphenyl or pyrrole moieties could also serve as traceless linkers.

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Strategies for cyclizations of novel peptides on solid supports

Cited by 11 publications

References 25 publications

Biological and conformational study of β‐substituted prolines in MT‐II template: steric effects leading to human MC5 receptor selectivity*

Biological and conformational study of β‐substituted prolines in MT‐II template: steric effects leading to human MC5 receptor selectivity*

Synthesis of Bicyclic Peptides

Polymer-supported syntheses of thiophene-containing compounds using a new type of traceless linker

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