We initially synthesized appropriately substituted various heterocycles as Thiazoles, Coumarin and Quinoline, Successful conjugation of PEG with biomolecule depends upon the chemical structure, molecular weight, steric hindrance, and the reactivity of the biomolecule as well as the polymer. In order to synthesize a bioconjugate, both chemical entities (i.e., the bioactive as well as the polymer) required to possess a reactive or functional group such as –COOH, –OH, –SH, or –NH2.Our strategy involves the synthesis of site-specific PEGylation is intensely being utilized to modify macromolecules, biomolecules, and surfaces. Protein PEGylation is able to address the fundamental issues of site-specific conjugation and high-efficiency conjugation. -NH2 group of Thiazoles, -OH and -COOH group of Coumarin and –SH group of Quinoline Based chalcones on their selective chemical reactivity and PEG reagents provide the best opportunity for efficient and site-specific PEGylation. The resultant series of Pegylated heterocyclic compounds were characterized by various techniques such as FTIR, 1HNMR, 13CNMR, Mass spectral data and elemental analysis.