Lexitropsins, Microgonotropens and House

I am writing a paper at the moment on some work my Honours student, Anthony Lo, carried out last year on an unusual distamycin mimic we synthesized. Distamycin A is a beautiful, crescent-shaped minor groove binder consisting of three amide-linked pyrroles and a couple of DNA-interacting groups on either end.

This molecule likes AT-rich regions of DNA, and the only thing more remarkable about its stunningly evolved fit is the sheer amount of wonderful science conducted to understand its mechanism of action and to develop variations in the basic structure so as to improve selectivity, or provide a predilection for GC bases, or fluoresce upon sequence binding. Dervan has been very active in developing a syntax for which components are needed to recognize a given sequence. The possibility of  “spelling out” a polyamide sequence recognizing any given DNA sequence has led to these molecules being called “lexitropsins,” presumably from “lex-” for “words” and “tropsin” for “turning”? Analogs containing alkylamines in place of alkyl groups of the lexitropsins are sometimes called “microgonotropens,” something I discovered from this review by Tom Bruice. Famous professors can start their biographies “Thomas C. Bruice dropped out of high school in the eleventh grade…”

I was digesting this vast and fascinating field when I was distracted by a House episode “Epic Fail”. The patient, a video games developer, is crowd-source-savvy and posts his symptoms online, rapidly receiving suggestions for tests and diagnoses in return. Part of the episode is the battle between the (small number of) highly trained doctors and the wisdom of the crowd. The patient even posts a reward, Innocentive-style. There are some interesting things here for anyone interested in open source, or open science. The plot alludes to the choice between following a well-trained expert or spending time sifting through many suggestions from the public. This is a recurrent objection that is raised about open source: “is it really worthwhile, given that one has to sift out junk?” and I am asked this on a fairly regular basis about our open chemistry project. The answer is complex and interesting and is the essential conflict between the Cathedral and the Bazaar. In the House episode the bazaar does rather well, with a caveat spoiler I won’t reveal.

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