Design, synthesis and conformational analysis of γ-turn peptide mimetics of bradykinin

Sato, Michito; Lee, Jessie Y.H.; Nakanishi, Hiroshi; Johnson, Michael E.; Chrusciel, R. A.; Kahn, Michaël

doi:10.1016/0006-291x(92)91296-3

Cited by 41 publications

(13 citation statements)

References 24 publications

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“…Several of the low-energy conformations exhibit yturns. This is very interesting, since they have been implicated as recognition motifs by the receptor [16,171. Thus conformations 6 and 9 exhibit a yturn involving Pro7, whereas conformations 1, 2 and 9 exhibit a y-turn involving Phe5.…”

Section: Comparison Of the Present Results With Available Experimentamentioning

confidence: 98%

Characterization of the conformational domains of bradykinin by computational methods

Pérez¹,

Sánchez²,

Centeno³

1995

Journal of Peptide Science

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The AMBER 4.0 force field was used to perform a characterization of the conformational profile of the nonapeptide bradykinin. A thorough conformational search was carried out using molecular dynamics as sampling technique, by computing cycles of high (900 K) and low (300 K) temperature trajectories. A total of 2400 minima were generated and subsequently clustered using the root-mean-square of the backbone dihedral angles as criterium. After the use of a tolerance value of 20 degrees, the conformations were clustered in 233 unique conformations with energies up to 40 kcal/mol above the lowest minimum. The analysis of the low-energy conformations indicate that the peptide exhibits a high tendency to adopt a beta-turn at the C-terminus and a propensity to adopt a bent structure at the N-terminus. These results are in agreement with the experimental evidence reported in the literature and provide detailed information necessary to understand the conformational preferences of the peptide.

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Section: Comparison Of the Present Results With Available Experimentamentioning

confidence: 98%

Characterization of the conformational domains of bradykinin by computational methods

Pérez¹,

Sánchez²,

Centeno³

1995

Journal of Peptide Science

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“…In order to understand whether the example described in the patent could be extrapolated to other cases, it would have been useful to see quantitative binding studies on individual bradykinin peptides to the bradykinin receptor before analysing the same peptides in the context of a mAb structure. This would be particularly relevant given that previous peptide mimetics of bradykinin have been well characterised [9]. Biochemical features of the ligand-receptor interaction would also have been informative, to understand whether the loss in affinity accompanying the reduction of a ligand to a peptide might be an issue.…”

Section: Biology and Actionmentioning

confidence: 99%

Site-specific structural modification of monoclonal antibodies for therapeutic application

2000

Expert Opinion on Therapeutic Patents

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“…The synthesis allows for the introduction of natural or unnatural amino acid side-chain functionality in either L or D configuration. Additionally, deletion of the second modular component 3 provides access to 7-turn mimetics [10],…”

Section: The Design and Synthesis Of Secondary-structuretemplated Libmentioning

confidence: 99%

Pharmaceutical applications of peptidomimetics

et al. 1996

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Nature has used a 'library approach' to constructing ligands for specific receptors and enzymes by combining a limited functional diversity of 20 amino acid side chains with a small array of secondary structure motifs -reverse turns, co-helices and [3-strands. The dissection of multidomain proteins into small synthetic conformationally restricted components is an important step in the design of low-molecular-weight nonpeptides that mimic the activity of the native protein. Mimetics of critical functional domains might possess beneficial properties with regard to specificity and therapeutic potential compared to the intact proteinaceous species. Combinatorial secondarystructure-templated libraries provide a powerful engine for the development of novel vaccines and pharmaceuticals.

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Design, synthesis and conformational analysis of γ-turn peptide mimetics of bradykinin

Cited by 41 publications

References 24 publications

Characterization of the conformational domains of bradykinin by computational methods

Characterization of the conformational domains of bradykinin by computational methods

Site-specific structural modification of monoclonal antibodies for therapeutic application

Pharmaceutical applications of peptidomimetics

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