|Name||Mr. Sami Abdulkadir|
|Organization or Institution||University of South Florida|
|Topic||Biochemistry / Chem Bio.|
Modulation of angiogenesis through rationally designed γ-AApeptide helical mimetic of VEGF
Sami Abdulkadir, Jianfeng Cai
University of South Florida
Angiogenesis, formation of new blood vessels from existing vascular network, is modulated mainly through vascular endothelial growth factors (VEGF). This is an important process in healing and development. Abnormalities in angiogenesis are related to several disease states, the most notable one being sustained angiogenesis that is a hallmark of cancer cells. Tumor vascular proliferation leads to tumor growth and metastasis and it is for this reason that the prospect of affecting this process has gained considerable interest in the fight against cancer. X-ray crystal structure of VEGF bound to its receptor-VEGFR indicate a helix structure on VEGF (residues 17 - 25) is an essential binding interface. Peptidomimetics offer great opportunity to rationally design binding interface mimics that can effectively modulate protein binding interactions. Our lab works in developing novel peptidomimetic scaffolds capable of various protein structural mimicry. Previous studies have established that γ-AApeptides adopt α-helix conformation. In this research we describe the design and synthesis of γ-AApeptide helical mimetics of the VEGF helix region. Preliminary testing on human cell lines show that the VEGF mimic synthesized promotes cell proliferation. Currently we are testing receptor binding and activity in human umbilical vein endothelial cells (HUVEC).