Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (588 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Guanidinium; Guanidine Sulfate; Sulfate, Guanidine; Guanidine Phosphate; Phosphate, Guanidine; Guanidine Monohydroiodine; Monohydroiodine, Guanidine; Guanidine Monohydrobromide.
Where it fits in the MeSH classification
- Broader topics
- Guanidines
Research landscape
PubMed indexes 5,798 records tagged with the MeSH heading “Guanidine” (counts retrieved 2026-10-31). 530 of them (9.1%) were published from 2020 onward, and the busiest period so far is through 1999 with 2,250 records.
Reviews account for 101 records (1.7%) and meta-analyses for 0. Randomized controlled trials number 1 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 2,250 |
| 2000-2009 | 1,832 |
| 2010-2019 | 1,186 |
| 2020 onward | 530 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 101 | 1.7% |
| Meta-analyses | 0 | 0.0% |
| Randomized controlled trials | 1 | 0.0% |
Method: PubMed query "Guanidine"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Differences in the pathways of proteins unfolding induced by urea and guanidine hydrochloride: molten globule state and aggregates | 2010 | Research article Design not recorded in structured metadata | 68 | cc by PMID 21152408 · DOI · PMC2994796 |
| The Structure of the Guanidine-II Riboswitch | 2017 | Research article Design not recorded in structured metadata | 61 | cc by PMID 28529131 · DOI · PMC5486947 |
| Potential benefits of sequential inhibitor-mutagen treatments of RNA virus infections | 2009 | Research article Design not recorded in structured metadata | 55 | cc by PMID 19911056 · DOI · PMC2771356 |
| Ionizable guanidine-based lipid nanoparticle for targeted mRNA delivery and cancer immunotherapy | 2025 | Research article Design not recorded in structured metadata | 14 | cc by PMID 41134881 · DOI · PMC12551712 |
Differences in the pathways of proteins unfolding induced by urea and guanidine hydrochloride: molten globule state and aggregates [1]
Abstract reading summary — source excerpts
- Opening excerpt
- It was shown that at low concentrations guanidine hydrochloride (GdnHCl) can cause aggregation of proteins in partially folded state and that fluorescent dye 1-anilinonaphthalene-8-sulfonic acid (ANS) binds with these aggregates rather than with hydrophobic clusters on the surface of protein in molten globule state.
- Closing excerpt
- So what was previously believed to be the molten globule state in the pathway of protein denaturation by GdnHCl, in reality, for some proteins represents the aggregates of partially folded molecules.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (99 words)
It was shown that at low concentrations guanidine hydrochloride (GdnHCl) can cause aggregation of proteins in partially folded state and that fluorescent dye 1-anilinonaphthalene-8-sulfonic acid (ANS) binds with these aggregates rather than with hydrophobic clusters on the surface of protein in molten globule state. That is why the increase in ANS fluorescence intensity is often recorded in the pathway of protein denaturation by GdnHCl, but not by urea. So what was previously believed to be the molten globule state in the pathway of protein denaturation by GdnHCl, in reality, for some proteins represents the aggregates of partially folded molecules.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 21152408 · DOI · PMC2994796
The Structure of the Guanidine-II Riboswitch [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The guanidine-II (mini-ykkC) riboswitch is the smallest of the guanidine-responsive riboswitches, comprising two stem loops of similar sequence.
- Closing excerpt
- One side of the pocket has an opening to the solvent, slightly lowering the specificity of ligand binding, and structures with bound methylguanidine, aminoguanidine, and agmatine show how this is possible.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (122 words)
The guanidine-II (mini-ykkC) riboswitch is the smallest of the guanidine-responsive riboswitches, comprising two stem loops of similar sequence. We have solved high-resolution crystal structures of both stem loops for the riboswitch from Gloeobacter violaceus. The stem loops have a strong propensity to dimerize by intimate loop-loop interaction. The dimerization creates specific binding pockets for two guanidine molecules, explaining their cooperative binding. Within the binding pockets the ligands are hydrogen bonded to a guanine at O6 and N7, and to successive backbone phosphates. Additionally they are each stacked upon a guanine nucleobase. One side of the pocket has an opening to the solvent, slightly lowering the specificity of ligand binding, and structures with bound methylguanidine, aminoguanidine, and agmatine show how this is possible.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28529131 · DOI · PMC5486947
Potential benefits of sequential inhibitor-mutagen treatments of RNA virus infections [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Lethal mutagenesis is an antiviral strategy consisting of virus extinction associated with enhanced mutagenesis.
- Closing excerpt
- The results may impact lethal mutagenesis-based protocols, as well as current antiviral therapies involving ribavirin.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (217 words)
Lethal mutagenesis is an antiviral strategy consisting of virus extinction associated with enhanced mutagenesis. The use of non-mutagenic antiviral inhibitors has faced the problem of selection of inhibitor-resistant virus mutants. Quasispecies dynamics predicts, and clinical results have confirmed, that combination therapy has an advantage over monotherapy to delay or prevent selection of inhibitor-escape mutants. Using ribavirin-mediated mutagenesis of foot-and-mouth disease virus (FMDV), here we show that, contrary to expectations, sequential administration of the antiviral inhibitor guanidine (GU) first, followed by ribavirin, is more effective than combination therapy with the two drugs, or than either drug used individually. Coelectroporation experiments suggest that limited inhibition of replication of interfering mutants by GU may contribute to the benefits of the sequential treatment. In lethal mutagenesis, a sequential inhibitor-mutagen treatment can be more effective than the corresponding combination treatment to drive a virus towards extinction. Such an advantage is also supported by a theoretical model for the evolution of a viral population under the action of increased mutagenesis in the presence of an inhibitor of viral replication. The model suggests that benefits of the sequential treatment are due to the involvement of a mutagenic agent, and to competition for susceptible cells exerted by the mutant spectrum. The results may impact lethal mutagenesis-based protocols, as well as current antiviral therapies involving ribavirin.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 19911056 · DOI · PMC2771356
Ionizable guanidine-based lipid nanoparticle for targeted mRNA delivery and cancer immunotherapy [4]
Abstract reading summary — source excerpts
- Opening excerpt
- The development of lipid nanoparticle (LNP) systems has largely advanced RNA therapeutics, particularly mRNA-based cancer immunotherapy.
- Closing excerpt
- These findings underscore the potential of guanidine-LNPs as a highly promising platform for organ-targeted mRNA delivery and cancer immunotherapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
The development of lipid nanoparticle (LNP) systems has largely advanced RNA therapeutics, particularly mRNA-based cancer immunotherapy. Conventional amine-LNPs, designed for hepatic RNA delivery, face challenges in targeting lymphoid organs effectively and maximize antigen presentation. In this study, we present the development of pH-responsive ionizable guanidine-LNPs (G-LNPs). Our cholesterol-free G-LNP system enables efficient delivery of mRNA to the spleen following intravenous administration. Notably, while both amine-LNPs and G-LNPs can deliver mRNA to the spleen, G-LNPs exhibit a unique ability to preferentially target antigen-presenting cells, leading to significantly enhanced antigen presentation and robust T cell activation. mRNA vaccines formulated with G-LNPs elicited strong and antigen-specific immune responses, providing complete protection against tumor progression. In addition, intraperitoneal administration of G-LNPs enabled selective mRNA expression in the pancreas, showcasing the versatility of this delivery platform. These findings underscore the potential of guanidine-LNPs as a highly promising platform for organ-targeted mRNA delivery and cancer immunotherapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41134881 · DOI · PMC12551712
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Noncovalent binding between guanidinium and anionic groups: focus on biological- and synthetic-based arginine/guanidinium interactions with phosph[on]ate and sulf[on]ate residues [5]
- Research article The design of guanidinium-rich transporters and their internalization mechanisms [6]
- Research article Adaptive translocation: the role of hydrogen bonding and membrane potential in the uptake of guanidinium-rich transporters into cells [7]
- Research article Molecular recognition of oxoanions based on guanidinium receptors [8]
- Research article Role of solvation effects in protein denaturation: from thermodynamics to single molecules and back [9]
- Research article Molecular transporters: synthesis of oligoguanidinium transporters and their application to drug delivery and real-time imaging [10]
References
- Povarova OI, Kuznetsova IM, Turoverov KK. Differences in the pathways of proteins unfolding induced by urea and guanidine hydrochloride: molten globule state and aggregates. . 2010. PMID 21152408 · DOI · PMC2994796
- Huang L, Wang J, Lilley DMJ. The Structure of the Guanidine-II Riboswitch. . 2017. PMID 28529131 · DOI · PMC5486947
- Perales C, Agudo R, Tejero H, Manrubia SC, Domingo E. Potential benefits of sequential inhibitor-mutagen treatments of RNA virus infections. . 2009. PMID 19911056 · DOI · PMC2771356
- Zhang H, Liu D, Yang K, Liang Z, Li M. Ionizable guanidine-based lipid nanoparticle for targeted mRNA delivery and cancer immunotherapy. . 2025. PMID 41134881 · DOI · PMC12551712
- Schug KA, Lindner W. Noncovalent binding between guanidinium and anionic groups: focus on biological- and synthetic-based arginine/guanidinium interactions with phosph[on]ate and sulf[on]ate residues. Chem Rev. 2005. PMID 15720152 · DOI
- Wender PA, Galliher WC, Goun EA, Jones LR, Pillow TH. The design of guanidinium-rich transporters and their internalization mechanisms. Adv Drug Deliv Rev. 2008. PMID 18164781 · DOI · PMC2533582
- Rothbard JB, Jessop TC, Wender PA. Adaptive translocation: the role of hydrogen bonding and membrane potential in the uptake of guanidinium-rich transporters into cells. Adv Drug Deliv Rev. 2005. PMID 15722160 · DOI
- Blondeau P, Segura M, Pérez-Fernández R, de Mendoza J. Molecular recognition of oxoanions based on guanidinium receptors. Chem Soc Rev. 2007. PMID 17264923 · DOI
- England JL, Haran G. Role of solvation effects in protein denaturation: from thermodynamics to single molecules and back. Annu Rev Phys Chem. 2011. PMID 21219136 · DOI · PMC3211090
- Goun EA, Pillow TH, Jones LR, Rothbard JB, Wender PA. Molecular transporters: synthesis of oligoguanidinium transporters and their application to drug delivery and real-time imaging. Chembiochem. 2006. PMID 16972294 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.