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The mechanism of participation of a urea group in hydrolysis of a phosphonate ester in acidic solution was investigated. Participation of the oxygen center of the ureido group of 1 and 3 at the phosphonate center is consistent with (1) the high degree of facilitation of ester hydrolysis compared to molecules lacking the adjacent functional group, (2) the observation that species resulting from attack of proximal nitrogen atoms of 1 and 3 are more stable than their precursors, and (3) the observation that acidic, anhydrous media containing alcohols cause rapid transesterification. A detailed mechanistic examination suggests that the participation reaction involves initial formation of a pentacovalent phosphorus intermediate with the ratedetermining step overall being breakdown of the intermediate to expel the leaving alcohol. The potential involvement of Ophosphobiotin in adenosine 5'-triphosphate (ATP) dependent carboxylations in enzymic systems is considered with regard to these results, enzymic results from other laboratories, and stereochemical restrictions. It is concluded that all available experimental evidence is consistent with, but does not require, intermediate formation of O-phosphobiotin. Enzymic carboxylation of O-phosphobiotin, leading to formation of iV-carboxybiotin and phosphate, is considered in terms of the stereochemistry of displacement at the phosphorus center of phosphobiotin. An "adjacent" mechanism, not involving free carboxyphosphate, and an "in-line" mechanism, involving free carboxyphosphate are possible. Reactions not involving O-phosphobiotin are likely to involve "in-line" displacement by bicarbonate at the terminal phosphate residue of ATP, requiring inversion of configuration at phosphorus. Since formation of O-phosphobiotin should occur with inversion at phosphorus, and transfer to bicarbonate with inversion or retention, the route via O-phosphobiotin can account for net inversion or net retention at phosphorus.

Studies of the interaction specificities of L-lysyl-L-phenylalaninamide (1) and the diastereomeric dipeptide amide, L-lysyl-D-phenylalaninamide (2), with salmon sperm DNA reveal distinct differences in the binding site of the aromatic ring of the phenylalanine residue. The results of 1H nuclear magnetic resonance (NMR), spin-lattice relaxation rates, viscometric, and flow dichroism studies indicate the aromatic ring of 1 is "partially" inserted between base pairs of DNA whereas the aromatic ring of 2 points outward toward the solution. The terminal L-lysyl residue presumably interacts stereospecifically with DNA helix thus dictating the positioning of the aromatic ring of the C-terminal phenylalanine residue. In the accompanying paper (E. J. Gabbay et al. (1976), Biochemistry, following paper in this issue), the interaction of several oligopeptide amides (containing the N-terminal L-Lys-L-Phe residue) with DNA is examined. The results are found to be consistent with stereospecific binding of the terminal L-lysyl residue, and in addition, the evidence suggests that oligopeptides may bind to DNA via a modified single-stranded beta-sheet structure which is wrapped around the nucleic acid helix in a manner similar to that described by M. H. F. Wilkins (1956), Cold Spring Harbor Symp. Quant. Biol. 21, 75).

Proton magnetic resonance studies (1H NMR) of the interaction of oligopeptide amides of defined sequence (and containing the amino acid, phenylalanine) with salmon sperm DNA are reported. The extent of upfield chemical shifts, deltasigma, and signal line broadening of the aromatic protons (in the presence of excess DNA) are found to depend on the primary sequence and stereochemistry of alpha carbons of the amino acids in the oligopeptide amides. The results obtained with 21 different di-, tri-, tetra-, penta- and hexapeptide amides are found to be consistent with a model whereby the peptide assumes a slightly modified single-stranded beta-sheet structure which is wrapped around the nucleic acid helix in a manner similar to that described by M. H. F. Wilkins (1956), Cold Spring Harbor Symp. Quant. Biol. 21, 75).

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