It is possible to react but the product is an anhydride which is not very stable. The more common approach will be to react an amine on the protein with methacrylic acid using a coupling agent like DCC or EDC with NHS in water,

Anhydride can react directly with amine but are generally hydrolysed in aqueous solution

Carboxylic acid groups abound in amino acids. When a protein is built, the carboxylic acid groups in these monomers react with the amino groups to form the peptide or amide linkages in the polymeric protein chains leaving little amounts of carboxylic groups possibly present as terminal or end groups of the chains.

For small molecules of methacrylic acids, it is not easy for them to move with their –COOH groups and  reach the –COOH groups of the protein macromolecules because these small molecules have to “swim” in a viscous medium. Assuming that a –COOH group of the first became adjacent to a –COOH group of the second; they cannot react to form anhydride without heating (necessary to eliminate water). If heat is provided, probably the methacrylic acid will polymerize or each 2 molecules of it will react to give methacrylic anhydride.

If methacrylic anhydride approaches a protein,it will favor a reaction with amino group “that gives an amide” over a reaction with a –COOH. If an aqueous medium is used, methacrylic anhydride will be converted into methacrylic acid “with each molecule giving 2 molecules”.

This research topic is not an easy one but I do wish you success.

I would like to make the following  points on this question.

            CH2=CHCOOH   +   CH2=CHCOOH   ----->     CH2=CHCOOCH2CH2COOH

        4. Please check whether some similar reaction can take place in case of

            methacrylic acid.

Thank you all for your answer. I appreciate it and will consider it then on my experiments. Initially, I want to try to use the methacrylation of gelatin, where gelatin (type A, pI = 7-9) is reacted with methacrylic anhydride in a basic buffer (9.0) at 60 degC under inert atmosphere. After the reaction time of 2h, the byproduct methacryrlic acid reduces the pH and on this state I want to use EDC/NHS coupling (as suggested by Dr. Yang). Are there any tips on how to do the experiment ? How long would the EDC/NHS coupling last,and what are the key controlled parameters?

The carboxylic acid in a protein will not  react with methacrylic acid or methacrylic anhydride.