二肽基肽酶IV(DPP IV/CD26)激活的前体药物：一个成功的策略用于改进水溶性和口服生物活性

Title:Dipeptidyl-Peptidase IV (DPP IV/CD26)-Activated Prodrugs: A Successful Strategy for Improving Water Solubility and Oral Bioavailability

Volume: 22 Issue: 8

Author(s): Sonsoles Velazquez, Sonia de Castro, Alberto Diez-Torrubia, Jan Balzarini and María-Jose Camarasa

Affiliation:

关键词: 含氨基药物，CD26前体药物，二肽基肽酶IV，含羟基药物，口服生物活性，多肽，稳定性，水溶性。

摘要: In the search of novel enzyme-based prodrug approaches to improve pharmacological properties of therapeutic drugs such as solubility and bioavailability, dipeptidyl-peptidase IV (DPP IV, also termed as CD26) enzyme activity provides a previously unexplored successful prodrug strategy. This review covers key aspects of the enzyme useful for the design of CD26-directed prodrugs. The proof-of-concept of this prodrug technology is provided for amine-containing agents by directly linking appropriate di- (or oligo)peptide moieties to a free amino group of a non-peptidic drug through an amide bond which is specifically hydrolized by DPP IV/CD26. Special emphasis is also made in discussing the design and synthesis of more elaborated tripartite prodrug systems, for further extension of the strategy to hydroxy-containing drugs. The application of this technology to improve water solubility and oral bioavailability of prominent examples of antiviral nucleosides is highlighted.

Cite this article as:

Sonsoles Velazquez, Sonia de Castro, Alberto Diez-Torrubia, Jan Balzarini and María-Jose Camarasa , Dipeptidyl-Peptidase IV (DPP IV/CD26)-Activated Prodrugs: A Successful Strategy for Improving Water Solubility and Oral Bioavailability, Current Medicinal Chemistry 2015; 22 (8) . https://dx.doi.org/10.2174/0929867322666150114163449