Development of a cytokine analog with enhanced stability using computational ultrahigh throughput screening.

ABSTRACT: Granulocyte-colony stimulating factor (G-CSF) is used worldwide to prevent neutropenia caused by high-dose chemotherapy. It has limited stability, strict formulation and storage requirements, and because of poor oral absorption must be administered by injection (typically daily). Thus, there is significant interest in developing analogs with improved pharmacological properties. We used our ultrahigh throughput computational screening method to improve the physicochemical characteristics of G-CSF. Improving these properties can make a molecule more robust, enhance its shelf life, or make it more amenable to alternate delivery systems and formulations. It can also affect clinically important features such as pharmacokinetics. Residues in the buried core were selected for optimization to mini

SUBMITTER: Luo P 

PROVIDER: S-EPMC2373568 | biostudies-literature | 2002 May

REPOSITORIES: biostudies-literature