The partial retro-inverso modification: a road traveled together.
In the mid-1970s, Dr. Murray Goodman was interested in a reversed peptide bond as a surrogate to understand the functional role of the amide bond in aspartame, a dipeptide sweetener. Very soon, realizing the breath and potential of this modification, Murray expanded this activity into a full program and I was fortunate to be part of it. Together we formulated new concepts such as the partially modified retro-inverso and end-group modified retro-inverso transformations, tested hypotheses, generated novel nomenclature, developed synthetic routes, characterized the preferred conformations of the unique building blocks employed in this modification, the gem-diaminoalkyl and the C2-substituted malonyl residues, and studied the biological activity of retro-inverso isomers of bioactive peptides. In the early 1980s several laboratories initiated extensive research targeted at the retro-inverso modification. The revival of this field led to new applications, new methods of synthesis, and new insights on the conformational and topological properties of the retro-inverso modification. Among the fields that embraced the retro-inverso concept were immunology as pertains to subjects such as synthetic vaccines, immunomodulators, and diagnostic tools, and drug delivery field as pertains to targeted and nontargeted cell permeation vectors loaded with bioactive cargo. Doctor Murray Goodman's sudden death leaves behind not only family, friends, and colleagues, but also an impressive record of scientific achievements among which is the revival of the modern era of the retro-inverso transformation. Murray's numerous contributions, excellent leadership, enthusiastic promotion, and outstanding teachings in this field will carry and illuminate his memory far into the future.
Chorev
Michael
M
Harvard Medical School, Laboratory for Translational Research, One Kendall Square, Building 600, 3rd Floor, Cambridge, MA 02139, USA. michael_chorev@hms.harvard.edu
D000595:Amino Acid Sequence; D001218:Aspartame / Q000138:chemical synthesis / Q000737:chemistry / Q000266:history; D001812:Blood-Brain Barrier; D020650:Combinatorial Chemistry Techniques; D016503:Drug Delivery Systems; D049673:History, 20th Century; D006801:Humans; D007120:Immunochemistry; D007202:Indicators and Reagents; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000266:history* / Q000276:immunology; D011487:Protein Conformation; D013237:Stereoisomerism; D013549:Sweetening Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000266:history; D014481:United States
D007202:Indicators and Reagents; D010455:Peptides; D013549:Sweetening Agents; D001218:Aspartame