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Linear presentation of variable side-chain spacing in a highly diverse combinatorial library
V Krchnák1, A S Weichsel, D Cabel
1Selectide Corporation, Tucson, AZ, USA.
Peptide Research
|July 1, 1995
Summary
A novel synthetic compound library, the alpha, beta, gamma-library, was created using diamino acids and variable spacing to present pharmacophores. This library enables diverse compound generation and identification through peptide tagging for drug discovery.
Area of Science:
- Medicinal Chemistry
- Synthetic Chemistry
- Drug Discovery
Background:
- Designing diverse compound libraries is crucial for identifying novel drug candidates.
- Linear presentation of pharmacophores with variable spacing offers a unique approach to molecular design.
Purpose of the Study:
- To design and synthesize a novel synthetic library (alpha, beta, gamma-library) for presenting potential pharmacophores.
- To demonstrate the library's capability for generating diverse compounds and identifying their compositions.
Main Methods:
- A library scaffold was constructed using diamino acids linked by amide bonds via alpha- or side-chain amino groups.
- Diverse compounds were generated by acylating the remaining amino groups with various carboxylic acids.
- Peptide tags synthesized concurrently with library structures were used to identify compound compositions.
Main Results:
- The successful synthesis of individual compounds and a model library was achieved.
- The methodology allowed for appreciable diversity in the generated compounds.
- Peptide tagging provided accurate information on carboxylic acid coupling and scaffold attachment points.
Conclusions:
- The alpha, beta, gamma-library design is a viable strategy for creating diverse compound collections.
- This library approach facilitates the presentation of pharmacophores with controlled spacing and linkage.
- The integrated peptide tagging system enables efficient identification of synthesized compounds, supporting drug discovery efforts.