# Toward the Establishment of a Harmonized Physicochemical Profiling Platform for Therapeutic Oligonucleotides: A Case Study for Aptamers Where the Higher-Order Structure Influences Physical Properties

https://mdr.nims.go.jp/datasets/9886d20c-60e9-45e2-a6aa-7ce6af8965ca

## File

- [Manuscript_MolPharm_final.docx](https://mdr.nims.go.jp/filesets/7eb79dac-4d68-42cf-ac52-0ad9dfc5ae7b/download) ([Detail](https://mdr.nims.go.jp/filesets/7eb79dac-4d68-42cf-ac52-0ad9dfc5ae7b.md))

## Id

9886d20c-60e9-45e2-a6aa-7ce6af8965ca

## Local identifier



## Visibility

open_to_public

## State

published

## Created at

2024-10-07T11:11:43.516254Z

## Updated at

2025-06-14T23:30:25.971786Z

## Published at

2025-06-14T23:20:14.905316Z

## Doi

https://doi.org/10.48505/nims.4821

## First published url

https://doi.org/10.1021/acs.molpharmaceut.4c00177

## Date published

2024-07-01

## Recorded date published

2024-7-1

## Resource type

journal_article

## Manuscript type

accepted_manuscript

## Collection



## Title

- title: 'Toward the Establishment of a Harmonized Physicochemical Profiling Platform
    for Therapeutic Oligonucleotides: A Case Study for Aptamers Where the Higher-Order
    Structure Influences Physical Properties'
  title_type: original
  lang: en

## Description

- description: Oligonucleotides are short nucleic acids that serve as one of the most
    promising classes of drug modality. However, attempts to establish a physicochemical
    evaluation platform of oligonucleotides for acquiring a comprehensive view of
    their properties have been limited. As the chemical stability and the efficacy
    as well as the solution properties at a high concentration should be related to
    their higher-order structure and intra-/intermolecular interactions, their detailed
    understanding enables effective formulation development. Here, the higher-order
    structure and the thermodynamic stability of the thrombin-binding aptamer (TBA)
    and four modified TBAs, which have similar sequences but were expected to have
    different higher-order structures, were evaluated using ultraviolet spectroscopy
    (UV), circular dichroism (CD), differential scanning calorimetry (DSC), and nuclear
    magnetic resonance (NMR). Then, the relationship between the higher-order structure
    and the solution properties including solubility, viscosity, and stability was
    investigated. The impact of the higher-order structure on the antithrombin activity
    was also confirmed. The higher-order structure and intra-/intermolecular interactions
    of the oligonucleotides were affected by types of buffers because of different
    potassium concentrations, which are crucial for the formation of the G-quadruplex
    structure. Consequently, solution properties, such as solubility and viscosity,
    chemical stability, and antithrombin activity, were also influenced. Each instrumental
    analysis had a complemental role in investigating the higher-order structure of
    TBA and modified TBAs. The utility of each physicochemical characterization method
    during the preclinical developmental stages is also discussed.
  description_type: abstract
  lang: und

## Creator

- name: Shoko Takeuchi
  role: author
- name: Tomohiko Yamazaki
  role: author
  orcid: https://orcid.org/0000-0003-2136-8042
  organization: National Institute for Materials Science
  ror: https://ror.org/026v1ze26
- name: Katsutoshi Yamaguchi
  role: author
- name: Fusae Komura
  role: author
- name: Takahiro Tabata
  role: author
- name: Hirotaka Nishi
  role: author
- name: Satomi Azumai
  role: author
- name: Kanako Miura
  role: author
- name: Mai Hirokawa
  role: author
- name: Keisuke Ikemoto
  role: author
- name: Kohsaku Kawakami
  role: author
  orcid: https://orcid.org/0000-0002-3466-9365
  organization: National Institute for Materials Science
  ror: https://ror.org/026v1ze26

## Contact agent



## Publisher

organization: American Chemical Society (ACS)

## Managing organization



## Keyword

- subject: oligonucleotide
  schema: not_defined
- subject: higher-order structure
  schema: not_defined
- subject: thrombin aptamer
  schema: not_defined
- subject: G-quadruplex
  schema: not_defined
- subject: physicochemical profiling
  schema: not_defined

## Rights

- description: This document is the Accepted Manuscript version of a Published Work
    that appeared in final form in Molecular Pharmaceutics, copyright © 2024 American
    Chemical Society after peer review and technical editing by the publisher. To
    access the final edited and published work see https://doi.org/10.1021/acs.molpharmaceut.4c00177
  identifier: http://rightsstatements.org/vocab/InC/1.0/

## Other identifier(s)



## Data origin

- data_origin_type: other

## Embargo

start_date: 2024-06-13
end_date: 2025-06-15

## Journal

- title: Molecular Pharmaceutics
  issn: '15438392'
  volume: '21'
  issue: '7'
  start_page: 3471
  end_page: 3484

## Conference



## Related item



## Funding

- funder_name: Eisai Co., Ltd.
- funder_name: University of Tsukuba
- funder_name: Takeda Pharmaceutical Company
- funder_name: Astellas Pharma
- funder_name: National Institute for Materials Science
- funder_name: Sawai Pharmaceutical
- funder_name: Materials Open Platform for Pharmaceutical Science
- funder_name: Mitsubishi Tanabe Pharma Corporation
- funder_name: Daiichi-Sankyo

## Instrument



## Instrument operator



## Instrument managing organization



## Measurement method



## Specimen



## Chemical composition



## Structure for specimen



## Structural feature for specimen



## Specific property for specimen



## Process for specimen treatment



## Computational method



## Energy level/transition state



## Software



## Custom property



## Fileset

- id: 7eb79dac-4d68-42cf-ac52-0ad9dfc5ae7b
  filename: Manuscript_MolPharm_final.docx
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  size: 1281036
  md5: 07cf18f2965c9768ff01eab09d6e98d0

## Thumbnail

fileset_id: 7eb79dac-4d68-42cf-ac52-0ad9dfc5ae7b
filename: Manuscript_MolPharm_final.docx