Peptide Lead Optimization
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Peptide Lead Optimization

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Peptide lead optimization is to improve upon a lead molecule that demonstrates activity at a target of interest by optimizing its potency or selectivity at the target and its absorption, distribution, metabolism and elimination (ADME) properties. For a successful peptide lead optimization, access to a reliable in vitro assay system is of utmost importance. This allows for precise SAR evaluations based on the binding affinity of peptide analogs to the target protein.

In order to make a compound a drug sample, at least five basic attributes need to be considered including potency, bioavailability, duration, safety, and pharmaceutical acceptability.

How to optimize the peptide lead?

Creative Peptides has an experienced drug development team that can provide our customers with an optimized one-stop solution for peptide lead drugs. Our diverse peptide library design is based on molecular modeling and multi-parameter optimization, covering medicinal chemistry evaluation parameters such as biochemical potency, pharmacokinetics and pharmacodynamics.

  1. Chemical modifications of a lead peptide

Optimization of the lead can improve its efficacy, selectivity or pharmacokinetic parameters. For peptide lead compounds, effective chemical structural modifications allow the identification of amino acids in sequences that are critical for binding, as well as amino acid sites that increase affinity.

  1. Prodrug design

Using the principle of prodrugs, the pharmacokinetic properties of the lead compounds can be improved, such as increasing the metabolic stability of the drug, interfering with the transport characteristics, allowing the drug to target the target cells, improving the selectivity of the action, etc., but generally not increasing its activity.

  1. Peptide Libraries

The synthesis of peptide libraries mainly uses combinatorial chemistry, and its development provides a synthetic method for combinatorial chemistry, screening methods, library decoding and compound identification methods. Combinatorial chemistry is the integration of combinatorial synthesis and activity screening, including the design, synthesis, screening, and determination of compounds in a compound library. It is important to apply Peptide Libraries to the discovery and optimization of leads.

Reference:
[1] Srivastava, V. (Ed.). (2017). Peptide-based Drug Discovery: Challenges and New Therapeutics (Vol. 59). Royal Society of Chemistry.

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