Sato Aaron K, Viswanathan Malini, Kent Rachel B, Wood Clive R
Dyax Corporation, 300 Technology Square, Cambridge, MA 02139, USA.
Curr Opin Biotechnol. 2006 Dec;17(6):638-42. doi: 10.1016/j.copbio.2006.10.002. Epub 2006 Oct 17.
As potential therapeutics, peptides offer several advantages over small molecules (increased specificity) and antibodies (small size). Nevertheless, a number of key issues have hampered their use as drug candidates. A series of new technologies have recently been developed that allow peptides to be viable drug candidates in areas usually restricted to protein therapeutics, such as monoclonal antibodies. These include the development of various types of peptide-conjugates that have lower rates of clearance and hence the potential to increase the exposure of peptide drug candidates in chronic diseases. Structural additions have also been made to peptides, including the use of unnatural amino acids, mainchain modifications and other novel substitutions, which have helped to improve peptide stability and further their therapeutic potential.
作为潜在的治疗药物,肽类相对于小分子(更高的特异性)和抗体(更小的尺寸)具有若干优势。然而,一些关键问题阻碍了它们作为候选药物的应用。最近开发了一系列新技术,使肽类能够在通常仅限于蛋白质治疗药物(如单克隆抗体)的领域成为可行的候选药物。这些技术包括开发各种类型的肽缀合物,其清除率较低,因此有可能增加肽类候选药物在慢性疾病中的暴露量。还对肽类进行了结构修饰,包括使用非天然氨基酸、主链修饰和其他新型取代,这有助于提高肽的稳定性并进一步提升其治疗潜力。