Evolution of Microphase Separation with Variations of Segments of Sequence-Controlled Multiblock Copolymers

Multiblock copolymers (MBCPs) are an emerging class of materials that are becoming more accessible in recent years. However, to date there is still a lack of fundamental understanding of their physical properties. In particular, the glass transition temperature (Tg) which is known to be affected by the phase separation has not been well characterized experimentally. To this end, we report the first experimental study on the evolution of the Tgs and the corresponding phase separation of linear MBCPs with increasing number of blocks while keeping the overall degree of polymerization (DP) constant (DP = 200). Ethylene glycol methyl ether acrylate (EGMEA) and tert-butyl acrylate (tBA) were chosen as monomers for reversible addition-fragmentation chain transfer polymerization to synthesize MBCPs. We found the Tgs (as measured by differential scanning calorimetry) of EGMEA and tBA segments within the MCBPs to converge with increasing number of blocks and decreasing block length, correlating with the loss of the heterogeneity as observed from small-angle X-ray scattering (SAXS) analysis. The Tgs of the multiblock copolymers were also compared to the Tgs of the polymer blends of the corresponding homopolymers, and we found that Tgs of the polymer blends were similar to those of the respective homopolymers, as expected. SAXS experiments further demonstrated microphase separation of multiblock copolymers. This work demonstrates the enormous potential of multiblock architectures to tune the physical properties of synthetic polymers, by changing their glass transition temperature and their morphologies obtained from microphase separation, with domain sizes reaching under 10 nm

Computational Characterization of the Binding Properties of the HIV1-Neutralizing Antibody PG16 and Design of PG16-Derived CDRH3 Peptides

PG16 is a broadly neutralizing antibody that binds to the gp120 subunit of the HIV-1 Env protein. The major interaction site is formed by the unusually long complementarity determining region (CDR) H3. The CDRH3 residue Tyr100H is known to represent a tyrosine sulfation site; however, this modification is not present in the experimental complex structure of PG16 with full-length HIV-1 Env. To investigate the role of sulfation for this complex, we modeled the sulfation of Tyr100H and compared the dynamics and energetics of the modified and unmodified complex by molecular dynamics simulations at the atomic level. Our results show that sulfation does not affect the overall conformation of CDRH3, but still enhances gp120 interactions both at the site of modification and for the neighboring residues. This stabilization affects not only protein–protein contacts, but also the interactions between PG16 and the gp120 glycan shield. Furthermore, we also investigated whether PG16-CDRH3 is a suitable template for the development of peptide mimetics. For a peptide spanning residues 93-105 of PG16, we obtained an experimental EC50 value of 3nm for the binding of gp120 to the peptide. This affinity can be enhanced by almost one order of magnitude by artificial disulfide bonding between residues 99 and 100F. In contrast, any truncation results in significantly lower affinity, suggesting that the entire peptide segment is involved in gp120 recognition. Given their high affinity, it should be possible to further optimize the PG16-derived peptides as potential inhibitors of HIV invasion