| dc.description.abstract | The structure, assembly and action of proteins critically depend upon non?covalent interactions. A programme aimed at elucidating the atomic details of such interactions using an approach involving the preparation and X?ray analysis of crystalline complexes of amino acids and peptides has been in progress in this laboratory for the last couple of decades. In the course of executing the programme it was realized that the interactions and aggregation patterns observed in the complexes have implications to chemical evolution as well. Since then the main theme of the work has been the role of molecular interactions and aggregation in chemical evolution with special reference to prebiotic polymerisation, chiral effects and self?assembly, although the results have also been of considerable general interest in relation to various aspects of biomolecular interactions and aggregation. A review of the work that has already been carried out in the programme is presented in the introductory chapter as a prelude to describing the author’s contribution to it. The methods used for crystallization and X?ray analysis are summarised in the next chapter.
The current focus of the work involving crystalline complexes is on those between amino acids and other simple molecules that are believed to have existed in the prebiotic milieu. In this context, complexes involving succinic acid have already been analysed. The author’s work, which has been discussed in the subsequent chapters, primarily consisted of the structure determination of the acetic acid complexes of histidine and a comparative study of the available amino acid complexes with this carboxylic acid, and the analysis of the formic acid complexes of DL? and L?arginine, lysine and histidine, and the glycolic acid complexes of DL? and L?histidine. The amino acid molecules in all the complexes are positively charged zwitterions. The carboxylic acid is deprotonated and negatively charged in all but one case. The L?histidine complex of formic acid contains a formic acid molecule and a formate ion.
Among other things, the structures provide further evidence for the conformational variability of amino acid side chains. They contain several specific interactions and characteristic interaction patterns with varying degrees of similarity to those observed earlier in the programme. The structures permit the delineation of the effects of the presence of other molecules on amino?acid aggregation. Despite differences in the observed aggregation patterns, the primary mode of arginine–carboxylic acid interactions is substantially invariant in the arginine complexes of succinic, acetic and formic acids. The complexes also demonstrate the relative invariance of certain aggregation and interaction patterns involving lysine. The patterns in histidine complexes, however, appear to exhibit considerably higher variability than those in the complexes of arginine and lysine. A comparison between the respective DL and L amino?acid complexes provides interesting insights into the effect of chirality on molecular aggregation. The crystallization experiments involving glycolic acid and histidine present an unusual case of chiral separation of amino acids through interactions with an achiral molecule, a possible structural rationale for which is provided by the corresponding complexes.
In the course of the work, the crystals of DL?arginine and DL?proline, the structures of which have not been reported so far, were also analysed. The structure of DL?arginine has been discussed in the chapter dealing with the formic?acid complexes of arginine, while that of DL?proline forms the subject matter of an appendix.
While pursuing the project on crystalline complexes of amino acids as his main effort, the author also participated in the protein crystallography programme in the laboratory. He prepared and characterised crystals of artocarpin, a mannose?specific lectin from the seeds of jackfruit, and carried out other preliminary studies on them. This work is presented in another appendix. | |
