【摘 要】
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Lipidization is a chemical modification that can increase the lipophilicity of polypeptide molecules.However,there are three general limitations in conventional lipidization methods that involve a dir
【机 构】
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University of Southern California School of Pharmacy USA
【出 处】
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2008中国深圳蛋白质和多肽科学大会
论文部分内容阅读
Lipidization is a chemical modification that can increase the lipophilicity of polypeptide molecules.However,there are three general limitations in conventional lipidization methods that involve a direct conjugation of lipid molecules to a polypeptide.First,lipids and polypeptides are usually incompatible in reaction solutions.Second,a direct lipid-polypeptide conjugation will very likely yield a product that is insoluble in water.Third,lipidized polypeptides will generally lose their biological activity.To avoid these problems,we have developed methods for the preparation of fatty acid-polypeptide conjugates that can be carried out in an aqueous solution and can regenerate the original active polypeptides in tissues or blood.The conjugation methods are named "reversible aqueous lipidization" (REAL).Generally,REAL-modified polypeptides exhibit an increase in stability,plasma half-life,liver targeting,and/or oral bioavailability.Several therapeutic peptides and proteins,including calcitonin,Leu-enkephalin and interferon have been lipidized using the REAL technology and have demonstrated a significant improvement in their therapeutic efficacy.
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