Advances in peptide chemistry

Protein synthesis is nowadays achieved through molecular biology techniques: the relevant gene is cloned in an appropriate vector, over-expressed with e.g. a poly-histidine tag, and then purified through high affinity chromatography. Peptide chemistry is therefore often forgotten by biochemists, unless we need to order a short customized peptide from a commercial source.
Danishefsky et al. have now combined solid phase peptide synthesis, native chemical ligation and metal-free dethyilation to synthesize a number of analogues of human parathormone. Their strategy afforded native parathormone with higher purity than obtained from commercial sources, as well as pure analogues not achievable by any other means. These analogues were shown to be much more stable (10% decomposition in 7 days) than parathormone ,(>90% loss in 7 days), and to be as active as parathormone when injected to mice.
This is a very interesting work, which should pave the way towards the synthesis of long-lived synthetic peptide hormones, thus potentially decreasing the number of injections needed to control hormone levels in patients suffering from impaired endocrine function.

Drawing can be torture

Drawing complex three-dimensional molecules in two-dimensions can be a real torture. I am glad I have never had to draw anything as convoluted as palhinine A. Check the 3-D structure on the left, and try to draw it in less than 10 minutes in ChemDraw or ChemSketch. Good luck!