Title:Biphalin: The Foundation of Bivalent Ligands
Volume: 23
Issue: 29
Author(s): Scott M. Cowell, Yeon Sun Lee
Affiliation:
关键词:
Biphalin
摘要: Seldom in medicinal chemistry does one ligand present the ability to
study two separate phenomena in a pharmacological process. The discovery of
biphalin with other homodimeric ligands has given scientists a tool that not only
explores how to increase the efficacy of the ligand, but also explore the possible
interactions of hetero and homo dimerization of the receptors themselves. As a
straight ligand, biphalin has allowed scientists to increase efficacy by direct
modification of the residues to affect the message-address interactions with
receptors. This led to the exploration of ligand linkers to increase efficacy and it
was this modification of the linkers led to discoveries that suggested dimerization
of receptor system occurs as a secondary modulation of signal transduction. Even
more recently, exploration of the advances in linkers through the discovery of
bitopicity seems to modulate the actual receptors to increase the binding and
signal transdcution of the ligand. This is accomplished by possible slight
conformational changes in the receptors before binding of the ligand located at the
end of the linker. These advances were made by the work of the late Prof. Andrzej
W. Lipkowski. This review gives the foundation of biphalin and in turn celebrates
the contributions of Prof. Lipkowski made in this area.
