Paul H B, Welte T, Groneberg D A
Abteilung für Pneumologie, Medizinische Hochschule Hannover.
Pneumologie. 2005 Jul;59(7):461-9. doi: 10.1055/s-2004-870942.
The aerosolic administration of peptidomimetic drugs with a peptide backbone may play a crucial role in the future treatment of diseases. Especially rational drug design offers an option to synthesize new drugs that are carried by specific drug transporters. Out of the presently identified transporter proteins PEPT1 and PEPT2, the high-affinity transporter PEPT2 is found in the respiratory tract. The transporter possess 12 membrane spanning domains and catalyses an electrogenic uphill drug transport using a transmembrane electrochemical proton gradient. PEPT2 is expressed in the bronchial epithelium and in alveolar type II pneumocytes in human airways. Kinetic studies demonstrated that peptidomimetic compounds including antibiotic, antiviral and antineoplastic drugs are carried by PEPT2. The transporter also carries delta-aminolevulinic acid into the airways. This molecule can be used for the diagnostics of pulmonary neoplasms and for photodynamic therapy. Using the recently published data on minimal structural requirements for PEPT2-substrates, rational drug design may lead to a new generation of respiratory drugs and prodrugs, which are delivered to the airways via the molecular mechanisms of the PEPT2 transport system.
对具有肽骨架的拟肽药物进行气雾剂给药可能在未来疾病治疗中发挥关键作用。特别是合理药物设计为合成由特定药物转运体携带的新药提供了一种选择。在目前已鉴定的转运蛋白PEPT1和PEPT2中，高亲和力转运体PEPT2存在于呼吸道中。该转运体具有12个跨膜结构域，并利用跨膜电化学质子梯度催化电驱动的上坡药物转运。PEPT2在人类气道的支气管上皮细胞和II型肺泡上皮细胞中表达。动力学研究表明，包括抗生素、抗病毒和抗肿瘤药物在内的拟肽化合物由PEPT2携带。该转运体还将δ-氨基乙酰丙酸转运到气道中。这种分子可用于肺部肿瘤的诊断和光动力治疗。利用最近发表的关于PEPT2底物最小结构要求的数据，合理药物设计可能会导致新一代呼吸药物和前药的出现，它们通过PEPT2转运系统的分子机制被递送到气道中。
