Various versions of modified peptides/macrocycles have been getting a lot of buzz recently as an intriguing class of molecules that might be able to permeate cell membranes and modulate PPIs - a previously difficult drug target since small molecules are too small to make good contact, while antibodies/proteins are too big to make it past the membrane. A lot of big names - Bruce Booth, Greg Verdine, among other pharma folks - seem quite excited (see Booth's recent post: goo.gl and this piece in SciBX: goo.gl). However, it appears that at least stapled peptides might not be as good as promised, as Derek Lowe has pointed out (goo.gl) and as published in ACS Chem Bio (goo.gl). Thoughts?
