Oligonucleotide–Peptide Complexes: Phase Control by Hybridization

Vieregg, Jeffrey R.; Lueckheide, Michael; Marciel, Amanda B.; Leon, Lorraine; Bologna, Alex J.; Rivera, Josean Reyes; Tirrell, Matthew V.

doi:10.1021/jacs.7b03567

Oligonucleotide–Peptide Complexes: Phase Control by Hybridization

Journal Article · Tue Jan 09 00:00:00 UTC 2018 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.7b03567· OSTI ID:1461292

^[1]; ^[2]; Marciel, Amanda B. ^[1]; Leon, Lorraine ^[3]; Bologna, Alex J. ^[1]; Rivera, Josean Reyes ^[4]; Tirrell, Matthew V. ^[5]

Univ. of Chicago, IL (United States). Inst. for Molecular Engineering
Univ. of Chicago, IL (United States). Dept. of Chemistry
Univ. of Central Florida, Orlando, FL (United States). Dept. of Materials Science and Engineering
Univ. of Puerto Rico at Rio Piedras, San Juan, PR (United States). Dept. of Biological Sciences
Univ. of Chicago, IL (United States). Inst. for Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States). Inst. for Molecular Engineering

When oppositely charged polymers are mixed, counterion release drives phase separation; understanding this process is a key unsolved problem in polymer science and biophysical chemistry, particularly for nucleic acids, polyanions whose biological functions are intimately related to their high charge density. In the cell, complexation by basic proteins condenses DNA into chromatin, and membraneless organelles formed by liquid-liquid phase separation of RNA and proteins perform vital functions and have been linked to disease. Electrostatic interactions are also the primary method used for assembly of nanoparticles to deliver therapeutic nucleic acids into cells. This paper describes complexation experiments with oligonucleotides and cationic peptides spanning a wide range of polymer lengths, concentrations, and structures, including RNA and methylphosphonate backbones. We find that the phase of the complexes is controlled by the hybridization state of the nucleic acid, with double-stranded nucleic acids forming solid precipitates while single-stranded oligonucleotides form liquid coacervates, apparently due to their lower charge density. Adding salt "melts" precipitates into coacervates, and oligonucleotides in coacervates remain competent for sequence-specific hybridization and phase change, suggesting the possibility of environmentally responsive complexes and nanoparticles for therapeutic or sensing applications.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1461292

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 5 Vol. 140; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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