Noncovalent interactions of small biological molecules studied by electrospray ionization mass spectrometry

The formation of non-covalent supramolecular assemblies plays a critical role in stabilization (tertiary protein structure and DNA base pairing), recognition (enzyme-substrate, antibody-antigen, drug-target), and regulation (activation, deactivation, signaling) in biological systems. A systematic study of the clustering of the natural amino acids under both positive and negative mode electrospray ionization mass spectrometry begun in 1998, has resulted in publications reporting on the clustering of arginine, serine, and nucleobases in detail with preliminary discussions on phenylalanine, cysteine, and glutamic acid. Serine forms a magic number protonated octamer that dominates its electrospray mass spectrum. This octamer is strongly homochiral and mixed clusters of serine and homoserine and cysteine of the same chirality also give stable octamers. The dissociation behavior of the cluster suggests that it is comprised of serine dimer units and ab initio calculations suggest that it has a drum-shaped structure. Associated with the octamer are metaclusters, which are clusters of clusters. The addition of alkali and ammonium cations results in a significant increase in the self-aggregation of the nucleobases and in the discovery of uniquely stable magic number clusters. Sodium adducts of guanine, thymine, and uracil preferentially take the form of tetrameric (quartet) clusters. These gas phase results correlate with previously reported sodium stabilized guanosine, thymine, and uracil quartet structures responsible for telomere stabilization. In the presence of potassium, cesium, or ammonium cations, pentameric magic number pentameric clusters are formed with thymine and uracil