Research Summary

Synthetic Alpha-Helical Pores: Engineering, Assembly, and Applications

Protein pores are emerging as promising candidates for synthetic nanobiotechnology applications. Beta barrels and DNA pores have been engineered extensively, but the design and assembly of alpha-helical transmembrane pores are challenging. Fabrication of alpha-helix pores of sophisticated structures that selectively conduct small molecules could lead to a new class of nanopore sensors. Here, simple peptide synthesis allowed us to build structurally stable alpha-helical transmembrane pores of superior chemical tunability, stability, and selectivity, which might be challenging to attain with natural membrane pores.

Our latest research established the construction of the first stable and functional transmembrane pores composed of synthetic D-amino acid peptides.

Our current research targets the therapeutic possibilities of synthetic alpha-helical pores, constructing synthetic ion channels, and developing dimeric nanopores for single molecule sensing studies.

Selected references

1. Krishnan R.S, K Jana, Shaji AH, KS Nair, AD Das, D Vikraman, H Bajaj, U Kleinekathöfer, Mahendran KR. Assembly of Transmembrane Pores from Mirror-Image Peptides. Nature Communications. 2022. (doi: 10.1038/s41467-022-33155-6)
2. Krishnan R.S, Puthumadathil N, Shaji AH, Kumar KS, Mohan G, Mahendran KR. Designed alpha-helical barrels for charge-selective peptide translocation. Chemical Science. 2021. (doi: 10.1039/D0SC04856A)
3. Krishnan R.S, Satheesan R, Puthumadathil N, Kumar KS, Jayasree P, Mahendran KR. Autonomously assembled synthetic transmembrane peptide pores. Journal of the American Chemical Society. 2019. (doi: 10.1021/jacs.8b09973)

Engineered Biological Pores: Biosensing to Nanomedicine

Our research focuses on the molecular basis of substrate translocation across a specialized specific bacterial membrane pore CymA, which has the 15-residue segment inside the pore barrel, restricting its diameter and generating a sophisticated architecture. The intrinsic cation selectivity of the porin, with its peculiar interior geometry, makes CymA an interesting membrane transporter to work with. In our previous study, the potentiality of CymA as complex sugars nanopore sensor is well explored.

Our current research aims to introduce CymA as a target system to develop potential antimicrobial agents against gram-negative pathogens.

1. Vikraman D, Satheesan R, Kumar KS, Mahendran KR. Nanopore passport control for substrate-specific translocation. ACS Nano. 2020. (doi: 10.1021/acsnano.9b09408)
2. Vikraman D, Satheesan R, Rajendran M, Kumar N, Johnson JB, Krishnan RS, Mahendran KR*. Selective Translocation of Cyclic Sugars Through Dynamic Bacterial Transporter. ACS Sensors. 2022, 7, 6, 1766-1776.
3. Remya S, Krishnan R S, Mahendran KR*. Controlling Interactions of Cyclic Oligosaccharides with Hetero-oligomeric Nanopores: Kinetics of Binding and Release at the Single-Molecule Level. Small. 2018. 14 (32), 1801192.