CAKE, K.

OCT 31 1973

Dr. Ronald Cape

Cetus Corporation

600 Bancroft Way

Berkeley, California 94710

Dear Ron:

You will recall that some time ago one point I
did bring up with you, the idea of an essentially
empirical search for compounds that would have anti-
sickling activity. This could very well involve a
variety of substances from natural sources, chemical
random syntheses, or what I would focus on more spe-
cifically now: random hydrolysates of existing hemo-
globins or mixtures of allogopeptide sequences pro-
duced synthetically and at least partly analogous to
the hemoglobin molecules.

What provokes me to bring this question up again
is a fascinating series of articles in the New England
Journal of Medicine that began with the October 5th
issue*. There are lots of prescriptions there for
invitro assays for the kinds of activity that would be
useful as well as an excellent definition of the physi-
cal-chemical parameters being sought. Beyond that, Tony
Cerami's group here, potentially offexs the best possi-
ble situation for clinical testing of material that had
been successfully worked out up to that point.

One could, of course, think of using cloned biosyn-
thetic peptide sequences, with randomization by mutation,

especially in view of the fact that globin sequences have
long since been spliced into prokaryotic DNA.

Yours sincerely,

Joshua Lederberg

* See especially 10/19

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