Prodrug Design Targeting Intestinal PepT1 for Improved Oral Absorption: Design and Performance

Title:Prodrug Design Targeting Intestinal PepT1 for Improved Oral Absorption: Design and Performance

Volume: 14 Issue: 6

Author(s): Youxi Zhang, Jin Sun, Yongbing Sun, Yongjun Wang and Zhonggui He

Affiliation:

Keywords: Oligopeptide transporter 1, oral absorption, prodrugs, substrates structure specificity.

Abstract: Oligopeptide transporter 1 (PepT1) plays an essential role in the oral absorption of di-and tripeptides from the digestion of ingested protein. PepT1 has become a striking prodrug-designing target recently, since some poorly absorbed drugs can be modified as peptidomimetic prodrugs targeting intestinal PepT1 to improve membrane permeability, and eventually oral absorption of the parent drug. However, little and no comprehensive attempts have been made to especially focus on the recent developments of prodrugs targeting intestinal PepT1. This article summarized biology, transport mechanism, structure-transport requirements for PepT1 and significant advances on the PepT1-targeted prodrugs within the two decades. The article also aimed to highlight some inspirations and knowledge on the multifunctional PepT1-targeted design, which are necessary for obtaining optimal prodrug candidates. That is the requirements of multifunctional rational PepT1 prodrugs include enough binding affinity for PepT1, controlled or targeted release of parent drug, escapement from P-gp mediated efflux and enhanced chemical/metabolic stability. Several types of peptidomimetic prodrugs reported recently were discussed in detail in this review.

Cite this article as:

Zhang Youxi, Sun Jin, Sun Yongbing, Wang Yongjun and He Zhonggui, Prodrug Design Targeting Intestinal PepT1 for Improved Oral Absorption: Design and Performance, Current Drug Metabolism 2013; 14 (6) . https://dx.doi.org/10.2174/1389200211314060004