; R o o t E n t r y F C o m p O b j b W o r d D o c u m e n t O b j e c t P o o l 6 7 8 9 : ; < = > ? F Microsoft Word 6.0 Document MSWordDoc Word.Document.6 ; @ @ @ p @ Oliver 9508066 The primary objective of this research is to demonstrate that peptides can be synthesized from suitably derivatized and aminoacylated nucleotides which are suspended as a monolayer film at a water/air interface. Successful peptide synthesis at a monolayer surface may be a good mimic for ribosomal peptide synthesis as well as an efficient method to synthesize certain peptides. The formation of amide bonds from ester bonds is energetically downhill. However, biological systems find it necessary to catalyze peptide synthesis from activated amino acids with proteins or protein/RNA complexes. The catalysts perform at least two functions. The first role is to accelerate amide bond formation so that it competes with non-enzymatic hydrolysis of the activated amino acids. In addition the catalyst imposes order on the synthesis so that only a defined polymer is produced. We have now demonstrated that lipid derivatized nucleotides form monolayer films and these films can be compressed to densities similar to those seen in solids. This provides a compelling motivation to investigate the possibi lity of synthesizing peptide bonds at the monolayer. Nucleotides conjugated to lipids at the 5'-phosphate and aminoacylated at the 2',3'-position will be used to form a monolayer film. The surface pressure and packing density in the monolayer can be controlled by physically changing the surface area of the interface. At high packing densities we expect to see amide bond fomlation with rates higher than background hydrolysis. It is expected that the results obtained from this research will be both general and important, with significant implications for enzyme mechanisms and chemical peptide synthesis. %%% The goal of this award is to demonstrate that polypeptides can be synthesized in a non-enzymatic system at rates approaching those seen with ribosomes. We intend to synthesize derivatives of amino acids which will incorporate physical characteristics required to lock them at an air-water interface. Reaction rates at this interface will be controlled by varying the surface pressure andl thus the density of the amino acid derivatives. Infrared spectroscopy will be used to monitor the progress of the reaction. These preliminary experiments coupled with methods to preorganize the amino acid derivatives may allow us to design a method of rapidly synthesizing polypeptides of defined sequence. *** @ @ ; Oh +' 0 $ H l D h S u m m a r y I n f o r m a t i o n ( 5 R:WWUSERTEMPLATENORMAL.DOT jack cohen jack cohen @ { R @ G @ ug @ u Microsoft Word 6.0 7 e = e j j j j j j j g = ) I T ( g j g j j j j ~ j j j j a Oliver 9508066 The primary objective of this research is to demonstrate that peptides can be synthesized from suitably derivatized and aminoacylated nucleotides which are suspended as a monolayer film at a water/air interface. Successful peptide synthesis at a monolayer surface may be a good mimic for ribosomal peptide synthesis as well as an efficient method to synthesize certain peptides. The formation of amide bonds from ester bonds is energetically downhill. However, biological systems find it necessary to catalyze peptide synthesis from activated amino acids wit
