ORGN 347 |
| There is growing interest in biomimetic polymer systems with sequence- and length-specificity and an ability to fold into ordered three-dimensional conformations, and which offer greater in vivo stability and greater chemical diversity than polypeptides. Toward this end we are studying and developing poly-N-substituted glycines, or peptoids, as a class of sequence-specific, peptidomimetic oligomers that can be synthesized by a high-yielding, solid-phase protocol – similar to the way polypeptides are made – and that are resistant to protease degradation. Recently we have focused on developing structured polypeptoids as biostable mimics of helical peptides of therapeutic interest. We have synthesized, purified, and characterized helical polypeptoids up to 22 monomers in length, which by virtue of their biomimetic sequences and amphipathic structures show excellent mimicry of the lung surfactant proteins (SP) and of antimicrobial peptides such as magainin. The development of functional, biostable SP mimics promises to enable the development of a synthetic, biomimetic lung surfactant replacement for safe treatment of respiratory distress syndrome in premature infants, and which can be used as a vehicle for pulmonary drug delivery in children and adults. In such an exogenous pulmonary surfactant replacements, we show that close mimicry of the sequence patterning of lung surfactant proteins in peptoid foldamers is shown to be key to proper function both in vitro and in vivo. |
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Ralph F. Hirschmann Award in Peptide Chemistry: Symposium in Honor of Samuel H. Gellman
1:15 PM-5:00 PM, Tuesday, March 27, 2007 McCormick Place Lakeside -- Room E451A/B, Level 4, Oral
Division of Organic Chemistry |