Sanford Burnham Prebys Medical Discovery Institute La Jolla, California and Impilo Therapeutics, Inc., San Diego, CA, USA.
Matrix Biol. 2024 Nov;133:57-63. doi: 10.1016/j.matbio.2024.08.003. Epub 2024 Aug 14.
This article recounts my journey as a scientist in the early days of extracellular matrix research through the discovery of fibronectin, the RGD sequence as a key recognition motif in fibronectin and other adhesion proteins, and isolation and cloning of integrins. I also discuss more recent work on identification of molecular "zip codes" by in vivo screening of peptide libraries expressed on phage, which led us right back to RGD and integrins. Many disease-specific zip codes have turned out to be based on altered expression of extracellular matrix molecules and integrins. Homing peptides and antibodies recognizing zip code molecules are being used in drug delivery applications, some of which have advanced into clinical trials.
本文通过纤维连接蛋白的发现、RGD 序列作为纤维连接蛋白和其他黏附蛋白的关键识别基序,以及整合素的分离和克隆,讲述了我作为一名细胞外基质研究早期科学家的历程。我还讨论了最近通过噬菌体表达的肽文库进行体内筛选来鉴定分子“邮政编码”的工作,这使我们回到了 RGD 和整合素。许多疾病特异性的邮政编码原来是基于细胞外基质分子和整合素的异常表达。识别邮政编码分子的归巢肽和抗体被用于药物输送应用,其中一些已进入临床试验。