Novel design of bicyclic β-turn dipeptides on solid-phase supports and synthesis of [3.3.0]-bicyclo[2,3]-leu-enkephalin analogues

Xuyuan Gu; Jinfa Ying; Richard S. Agnes; Edita Navratilova; Peg Davis; Gannon Stahl; Frank Porreca; Henry I. Yamamura; Victor J Hruby

doi:10.1021/ol0488183

Novel design of bicyclic β-turn dipeptides on solid-phase supports and synthesis of [3.3.0]-bicyclo^[2,3]-leu-enkephalin analogues

Xuyuan Gu, Jinfa Ying, Richard S. Agnes, Edita Navratilova, Peg Davis, Gannon Stahl, Frank Porreca, Henry I. Yamamura, Victor J Hruby

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

20 Scopus citations

Abstract

(Chemical Equation Presented) External bicyclic β-turn dipeptide mimetics provide an excellent design approach that can offer a rich chiral ensemble of structures with different backbone conformations. We report herein a novel design of a convergent combinatorial synthetic methodology, which is illustrated by the solid-phase synthesis of a series of [3.3.0]-bicyclo ^[2,3]-Leu-enkephalin analogues. The reactions were optimized and the epimeric configurations were determined by 2D NMR spectroscopy. Biological assays show that these analogues have more potent δ binding affinity and bioactivity for δ vs μ opioid receptor, which may be related to the different conformations preferred by these analogues in our modeling studies.

Original language	English (US)
Pages (from-to)	3285-3288
Number of pages	4
Journal	Organic Letters
Volume	6
Issue number	19
DOIs	https://doi.org/10.1021/ol0488183
State	Published - Sep 16 2004

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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abstract = "(Chemical Equation Presented) External bicyclic β-turn dipeptide mimetics provide an excellent design approach that can offer a rich chiral ensemble of structures with different backbone conformations. We report herein a novel design of a convergent combinatorial synthetic methodology, which is illustrated by the solid-phase synthesis of a series of [3.3.0]-bicyclo [2,3]-Leu-enkephalin analogues. The reactions were optimized and the epimeric configurations were determined by 2D NMR spectroscopy. Biological assays show that these analogues have more potent δ binding affinity and bioactivity for δ vs μ opioid receptor, which may be related to the different conformations preferred by these analogues in our modeling studies.",

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T1 - Novel design of bicyclic β-turn dipeptides on solid-phase supports and synthesis of [3.3.0]-bicyclo[2,3]-leu-enkephalin analogues

AU - Gu, Xuyuan

AU - Ying, Jinfa

AU - Agnes, Richard S.

AU - Navratilova, Edita

AU - Davis, Peg

AU - Stahl, Gannon

AU - Porreca, Frank

AU - Yamamura, Henry I.

AU - Hruby, Victor J

PY - 2004/9/16

Y1 - 2004/9/16

N2 - (Chemical Equation Presented) External bicyclic β-turn dipeptide mimetics provide an excellent design approach that can offer a rich chiral ensemble of structures with different backbone conformations. We report herein a novel design of a convergent combinatorial synthetic methodology, which is illustrated by the solid-phase synthesis of a series of [3.3.0]-bicyclo [2,3]-Leu-enkephalin analogues. The reactions were optimized and the epimeric configurations were determined by 2D NMR spectroscopy. Biological assays show that these analogues have more potent δ binding affinity and bioactivity for δ vs μ opioid receptor, which may be related to the different conformations preferred by these analogues in our modeling studies.

AB - (Chemical Equation Presented) External bicyclic β-turn dipeptide mimetics provide an excellent design approach that can offer a rich chiral ensemble of structures with different backbone conformations. We report herein a novel design of a convergent combinatorial synthetic methodology, which is illustrated by the solid-phase synthesis of a series of [3.3.0]-bicyclo [2,3]-Leu-enkephalin analogues. The reactions were optimized and the epimeric configurations were determined by 2D NMR spectroscopy. Biological assays show that these analogues have more potent δ binding affinity and bioactivity for δ vs μ opioid receptor, which may be related to the different conformations preferred by these analogues in our modeling studies.

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Novel design of bicyclic β-turn dipeptides on solid-phase supports and synthesis of [3.3.0]-bicyclo^[2,3]-leu-enkephalin analogues

Abstract

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