Alejandro Zaffaroni, a founder of Alza Corp. and DNAX ResearchInstitute, both of Palo Alto, Calif., may have scored again withhis latest venture. Netherlands-based Affymax N.V. Affymax'sPalo Alto research center has developed a technique, calledVery Large-Scale Immobilized Polymer Synthesis, or VLSIPS,that allows the rapid generation of up to 40,000 distinctcompounds on discrete sites located on a solid support 1.28centimeters square.
The technique and its potential uses are described in today'sissue of Science. Essentially, Affymax is applying the conceptbehind photolithography, or the use of light to direct theformation of circuits on a silicon chip, to building chemicalstructures on the surface of a glass "chip," Stephen Fodor, thecompany's senior scientist, told BioWorld.
The technology could bring big changes to drug design anddiagnostics. Affymax's biggest challenges may be to line upsufficient funding to develop the technology's potential.
The chip surface is covered with linker molecules withchemical groups to which amino acids, the building blocks ofpeptides, can bind. With each successive reaction cycle, adifferent amino acid, coupled to a photoreactive blockingcompound, is added to growing peptide chains. The blockinggroup prevents addition of another amino acid to the chain.
The chip used in the reported experiments can generate 1,024different peptides through masking of different regions of thechip in each cycle. Only those regions left unmasked areexposed to the laser light, which removes the photoreactiveblocking group and allows the new amino acid to be added tothe peptide chain.
For example, by masking different regions of the chip for threecycles, adding the amino acids A, B and C, VLSIPS generatesseven distinct peptides: A, AC, AB, ABC, B, BC, C. Standardpeptide synthesis techniques would generate only one peptide,ABC, in the same number of cycles.
Fodor said that Affymax has developed about 100 differentchemical building blocks, including all of the naturallyoccurring amino acids and DNA bases and a number ofchemically modified amino acids, with which to generate novelmolecules on the chip.
But the technology's potential impact lies in an ability torapidly screen the 1,024 different compounds for an ability tobind to a biologically active molecule, such as a receptor,monoclonal antibody or DNA sequence. Binding patterns can bethe basis for designing drug candidates, the presence of genemutations or the sequence of genetic material.
Affymax is looking for corporate partners to help funddevelopment of related therapeutic and diagnostic products. Italso plans a second-round financing of $15 million to $20million this year. A first round of $25 million, raised in late1989, should carry Affymax until mid-year, Zaffaroni said.
-- Cynthia Robbins-Roth Editor in Chief
(c) 1997 American Health Consultants. All rights reserved.