Evidence map›Paper›PMID 40454080›Full record

ArticleACS omega2025

High-Resolution HPLC for Separating Peptide-Oligonucleotide Conjugates.

Miyako Naganuma, Genichiro Tsuji, Misato Amiya, Reira Hirai, Yuki Higuchi, Naoko Hata, Saoko Nozawa, Daishi Watanabe, Taeko Nakajima, Yosuke Demizu

Abstract read
In one paragraph

Article in ACS omega, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Miyako NaganumaDivision of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan.
Genichiro TsujiDivision of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan.ORCID https://orcid.org/0000-0002-2826-3852
Misato AmiyaYMC CO., LTD., 59 Yonnotsubo-cho, Iwakuraminami, Sakyo-ku, Kyoto 606-0033, Japan.
Reira HiraiYMC CO., LTD., 59 Yonnotsubo-cho, Iwakuraminami, Sakyo-ku, Kyoto 606-0033, Japan.
Yuki HiguchiYMC CO., LTD., 59 Yonnotsubo-cho, Iwakuraminami, Sakyo-ku, Kyoto 606-0033, Japan.
Naoko HataYMC CO., LTD., 59 Yonnotsubo-cho, Iwakuraminami, Sakyo-ku, Kyoto 606-0033, Japan.
Saoko NozawaYMC CO., LTD., 59 Yonnotsubo-cho, Iwakuraminami, Sakyo-ku, Kyoto 606-0033, Japan.
Daishi WatanabeDivision of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan.
Taeko NakajimaYMC CO., LTD., 59 Yonnotsubo-cho, Iwakuraminami, Sakyo-ku, Kyoto 606-0033, Japan.
Yosuke DemizuDivision of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan.ORCID https://orcid.org/0000-0001-7521-4861

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Peptide-oligonucleotide conjugates (POCs) are chimeric molecules that combine the specificity of oligonucleotides with the functionality of peptides, improving the delivery and therapeutic potential of nucleic acid-based drugs. However, the analysis of POCs, particularly those containing arginine-rich sequences, poses major challenges because of aggregation caused by electrostatic interactions. In this study, we developed an optimized high-performance liquid chromatography (HPLC) method for analyzing POCs. Using a conjugate of DNA and nona-arginine as a model compound, we systematically investigated the effects of various analytical parameters, including column type, column temperature, mobile-phase composition, and pH. A column packed with C18 resin with wide pores combined with butylammonium acetate as the ion-pairing reagent and an optimal column temperature of 80 °C provided superior peak resolution and sensitivity. The optimized conditions gave clear separation of POCs from unlinked oligonucleotides and enabled the detection of nucleic acid fragments lacking an alkyne moiety as a linkage part, which is critical for quality control. Our HPLC method is robust and reproducible and substantially reduces the complexity, time, and cost associated with the POC analysis. The method may improve the efficiency of quality control in the production of POCs, thereby supporting their development as promising therapeutic agents for clinical applications.

Identifiers

PMID40454080
PMCPMC12120573

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.