Polymeric ADAM protein mimics interrogate mammalian sperm-egg binding

Area of Science:

• Reproductive Biology
• Biochemistry
• Polymer Science

Background:

• ADAM2 and ADAM3 are sperm proteins crucial for mammalian sperm-egg binding.
• Their specific roles are challenging to study due to interdependent expression in the testis.

Purpose of the Study:

• To design and synthesize multivalent probes for investigating gamete interactions.
• To elucidate the binding mechanisms of ADAM2 and ADAM3 mimics in fertilization.

Main Methods:

• Synthesis of polymer mimics containing glutamate-cysteine-aspartate (ECD) for ADAM2 and glutamine-cysteine-aspartate (QCD) for ADAM3 using ring-opening metathesis polymerization.
• Testing the inhibitory effects of homopolymers and copolymers on fertilization.
• Investigating the role of beta(1) integrin in the inhibition process.

Main Results:

• Polymers with 100 copies of ECD mimics were potent inhibitors of fertilization.
• QCD polymers showed similar structure-activity profiles but lower potency than ECD polymers.
• Both ECD and QCD polymers required beta(1) integrin for fertilization inhibition.
• Triblock copolymers demonstrated potencies correlating with their homopolymers, with no observed synergy between ECD and QCD mimics.

Conclusions:

• ADAM2 and ADAM3 binding sequences (ECD and QCD) interact with the same protein complex, which includes beta(1) integrin.
• Multivalent polymer mimics are effective tools for studying sperm-egg binding mechanisms.