Evidence map›Paper›PMID 32080860›Full record

ArticlePhotochemistry and photobiology2020

Site-specific Bioconjugation and Convergent Click Chemistry Enhances Antibody-Chromophore Conjugate Binding Efficiency.

Amissi Sadiki, Eric M Kercher, Haibin Lu, Ryan T Lang, Bryan Q Spring, Zhaohui Sunny Zhou

Open access · greenAbstract read
In one paragraph

Article in Photochemistry and photobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 16% of its field
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

21 citing papers in PubMed, 32 citations in OpenAlex.

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  20. Photoclick Chemistry: A Bright Idea.Chemical reviews · 2021
    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

6 authors at 1 institution in 2 countries.

Amissi SadikiDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, MA.ORCID 0000-0003-3117-5682
Eric M KercherTranslational Biophotonics Cluster, Northeastern University, Boston, MA.ORCID 0000-0002-4538-244X
Haibin LuDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, MA.
Ryan T LangTranslational Biophotonics Cluster, Northeastern University, Boston, MA.ORCID 0000-0002-6793-7717
Bryan Q SpringTranslational Biophotonics Cluster, Northeastern University, Boston, MA.ORCID 0000-0001-7332-7707
Zhaohui Sunny ZhouDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, MA.ORCID 0000-0003-1645-7411
Northeastern University · US

Funding

Protein Modification: Isoaspartic AcidR01GM101396 · NIGMS · NORTHEASTERN UNIVERSITY · PI ZHOU, ZHAOHUI SUNNY · 2012 to 2015
$1.1M
Online monitoring and image-guided treatment of chemoresistant micrometastasesK22CA181611 · NCI · NORTHEASTERN UNIVERSITY · PI SPRING, BRYAN QUILTY · 2015 to 2017
$559k
NCI NIH HHS K22 CA181611NIGMS NIH HHS R01 GM101396NIH HHS K22CA181611
6 · The paper itself

Abstract

Photosensitizer (PS)-antibody conjugates (photoimmunoconjugates, PICs) enable cancer cell-targeted photodynamic therapy (PDT). Nonspecific chemical bioconjugation is widely used to synthesize PICs but gives rise to several shortcomings. The conjugates are heterogeneous, and the process is not easily reproducible. Moreover, modifications at or near the binding sites alter both binding affinity and specificity. To overcome these limitations, we introduce convergent assembly of PICs via a chemo-enzymatic site-specific approach. First, an antibody is conjugated to a clickable handle via site-specific modification of glutamine (Gln) residues catalyzed by transglutaminase (TGase, EC 2.3.2.13). Second, the modified antibody intermediate is conjugated to a compatible chromophore via click chemistry. Utilizing cetuximab, we compared this site-specific conjugation protocol to the nonspecific chemical acylation of amines using N-hydroxysuccinimide (NHS) chemistry. Both the heavy and light chains were modified via the chemical route, whereas, only a glutamine 295 in the heavy chain was modified via chemo-enzymatic conjugation. Furthermore, a 2.3-fold increase in the number of bound antibodies per cell was observed for the site-specific compared with nonspecific method, suggesting that multiple stochastic sites of modification perturb the antibody-antigen binding. Altogether, site-specific bioconjugation leads to homogenous, reproducible and well-defined PICs, conferring higher binding efficiency and probability of clinical success.

Indexed as

Click ChemistryAcylationCell Line, TumorCycloaddition ReactionElectrophoresis, Polyacrylamide GelHumansImmunoconjugatesIsoelectric FocusingPhotosensitizing AgentsSpectrophotometry, UltravioletImmunoconjugatesPhotosensitizing Agents

Identifiers

PMID32080860
PMCPMC7386253
OpenAlexW3007855164

What OpenQuestion holds

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Registered trials

None linked

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.