Small Molecules 

Small molecules refers to molecules which generally have a MW of less than about 6 kDa. Many companies have libraries of small molecules, often fungal, bacterial, or algal extracts, which can be screened. Tan described a library with over two million synthetic compounds which is compatible with miniaturized cell based assay (J. Am. Chem. Soc. 1998, 120: 8 565-8566). There are numberous commerically available compound libraries such as Chembridge DIVERSet. Libraries are also avilable from academic investigators, such as the Diversity set from the NCI developmental therapeutics program. Rational drug design can be achieved based on known compounds (e.g., a known inhibitor of C5 such as an antibody) or by the use of crystal or solution structural information. Peptidomimetics can be compounds in which at least a porition of a subject polypeptide is modified and the three D structure of the peptidomimetic remains substanitally the same as that of the subject polypeptide. 

 Protein M

Grover (US 15/115,773, published as 2017/0320921) discloses a method of purifying immunoglobulin molecules using an amino acid sequence from Mycoplasma genitalium (MG281, aka “Protein M”). The Protein M is 556 amino acids and 50 kDa in size. It has a large domain of 360 amino acid resiudes that binds primarily to the variable light chain of the immunoglobulin was well as a binding site called the LRR-like motif. It also ahs a C-terminal domain with 115 amino acid resiudes that protrudes over the antibody binding site. In addition, Protein M contains a 16-36 amino acid transmembrane domain. Grover showed that a number of Perotein M homologs or orthologs from mycoplasmas and other species share functional and structural properties with protein MG281 and also developed several variants of Protein M that have similar or improved Ig binding proterins. For example, Protein M variants lacking the C terminal doamin retain the ability to bind to immunoglobulins. Also conserved residues can be substituted with non-polar amino acid residuesbinds to immunoglobulins. Variants can also lack the N temrinal membrane spanning region and still be capable of generically binding to immunoglobulins.