The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, 99mTc) radiopharmaceuticals

Ganguly, Tanushree; Kasten, Benjamin B.; Bučar, Dejan‐Krešimir; MacGillivray, Leonard R.; Berkman, Clifford E.; Benny, Paul D.

doi:10.1039/c1cc15451f

Cited by 29 publications

(34 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IR analysis showed the expected v CO stretching bands for the fac -[Re I (CO) 3 ] + core (2028 and 1903 cm −1 ) as well as the presence of the isothiocyanate group (2107 cm −1 ), and ESI-MS analysis was consistent with the desired complex (583.1 m / z ). While the NMR spectra of 5 showed singlets for the methylene protons of the DPA chelate as opposed to AB quartets seen with several other fac -[M I (CO) 3 (DPA)] complexes, 5,17 the downfield shifts of these protons in 5 (4.88 ppm) compared to the original ligand (3.79 ppm) indicated that metal complexation occurred at the DPA portion of the chelate as expected.…”

Section: Resultsmentioning

confidence: 65%

See 1 more Smart Citation

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M^I(CO)₃]⁺ (M = Re, ^99mTc) Complexes for Targeting uPAR in Prostate Cancer

Kasten¹,

Cheng

et al. 2015

Bioconjugate Chem.

Self Cite

View full text Add to dashboard Cite

Developing new strategies to rapidly incorporate the fac-[MI(CO)3]+ (M = Re, 99mTc) core into biological targeting vectors in radiopharmaceuticals continues to expand as molecules become more complex and as efforts to minimize nonspecific binding increase. This work examines a novel isothiocyanate-functionalized bifunctional chelate based on 2,2′-dipicolylamine (DPA) specifically designed for complexing the fac-[MI(CO)3]+ core. Two strategies (postlabeling and prelabeling) were explored using the isothiocyanate-functionalized DPA to determine the effectiveness of assembly on the overall yield and purity of the complex with amine containing biomolecules. A model amino acid (lysine) examined (1) amine conjugation of isothiocyanate-functionalized DPA followed by complexation with fac-[MI(CO)3]+ (postlabeling) and (2) complexation of fac-[MI(CO)3]+ with isothiocyanate-functionalized DPA followed by amine conjugation (prelabeling). Conducted with stable Re and radioactive 99mTc analogs, both strategies formed the product in good to excellent yields under macroscopic and radiotracer concentrations. A synthetic peptide (AE105) which targets an emerging biomarker in CaP prognosis, urokinase-type plasminogen activator receptor (uPAR), was also explored using the isothiocyanate-functionalized DPA strategy. In vitro PC-3 (uPAR+) cell uptake assays with the 99mTc-labeled peptide (8a) showed 4.2 ± 0.5% uptake at 4 h. In a murine model bearing PC-3 tumor xenografts, in vivo biodistribution of 8a led to favorable tumor uptake (3.7 ± 0.7% ID/g) at 4 h p.i. with relatively low accumulation (<2% ID/g) in normal organs not associated with normal peptide excretion. These results illustrate the promise of the isothiocyanate-functionalized approach for labeling amine containing biological targeting vectors with fac-[MI(CO)3]+.

show abstract

Section: Resultsmentioning

confidence: 65%

“…8–13 Among these reactions, isoxazole formation, 14 thioether formation, 15,16 and hydrazone generation have been successfully utilized in proof-of-concept studies with the fac -[M I (CO) 3 ] + core. 17 …”

Section: Introductionmentioning

confidence: 99%

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M^I(CO)₃]⁺ (M = Re, ^99mTc) Complexes for Targeting uPAR in Prostate Cancer

Kasten¹,

Cheng

et al. 2015

Bioconjugate Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In fact, they have been used as drug carriers, dermal fillers, detergents, and wound-healing supports. [29][30][31] Amongm any newly developed chemoselective ligations, [32][33][34] click reactions such as the copper-mediated 1,3-dipolar Huisgenc ycloaddition, [35,36] andh ydrazone formation relying on carbonyl functionality [7,37] have seen widespread use. [29][30][31] Amongm any newly developed chemoselective ligations, [32][33][34] click reactions such as the copper-mediated 1,3-dipolar Huisgenc ycloaddition, [35,36] andh ydrazone formation relying on carbonyl functionality [7,37] have seen widespread use.…”

Section: Concepts Of Difunctionalization Of Polysaccharides and Hydromentioning

confidence: 99%

“…In principle,t he chemistry chosen should allow either of the two functional groups (aldehyde and hydrazide) to be introduced into any of the chosen polysaccharides.F urthermore, ab iologically relevant ligand (L), namely, cRGDfK (7), was plan-ned to be attachedt ot he polysaccharide strand by utilizing as econd click reaction. The first reaction between two clickable strands provides hydrogels, and the second reaction introduces the biologically relevant ligand.…”

Section: Introductionmentioning

confidence: 99%

A Synthetic Toolbox for the In Situ Formation of Functionalized Homo‐ and Heteropolysaccharide‐Based Hydrogel Libraries

Dibbert

Krause

Rios-Camacho

et al. 2016

Chemistry A European J

View full text Add to dashboard Cite

A synthetic toolbox for the introduction of aldehydo and hydrazido groups into the polysaccharides hyaluronic acid, alginate, dextran, pullulan, glycogen, and carboxymethyl cellulose and their use for hydrogel formation is reported. Upon mixing differently functionalized polysaccharides derived from the same natural precursor, hydrazone cross-linking takes place, which results in formation of a hydrogel composed of one type of polysaccharide backbone. Likewise, hydrogels based on two different polysaccharide strands can be formed after mixing the corresponding aldehydo- and hydrazido-modified polysaccharides. A second line of these studies paves the way to introduce a biomedically relevant ligand, namely, the adhesion factor cyclic RGD pentapeptide, by using an orthogonal click reaction. This set of modified polysaccharides served to create a library of hydrogels that differ in the combination of polysaccharide strands and the degree of cross-linking. The different hydrogels were evaluated with respect to their rheological properties, their ability to absorb water, and their cytotoxicity towards human fibroblast cell cultures. None of the hydrogels studied were cytotoxic, and, hence, they are in principal biocompatible for applications in tissue engineering.

show abstract

“…PAH has been utilized to create stimuli-responsive hydrogels, 21 drug delivery systems, 22,23 ion exchange resins, 21 and glycopolymers. 24 The hydrazide moiety located along the backbone of the polymer is an effective conjugation site for many types of aldehyde-containing molecules, induding sugars with a reducing end.…”

Section: Introductionmentioning

confidence: 99%

Versatile Methodology for Glycosurfaces: Direct Ligation of Nonderivatized Reducing Saccharides to Poly(pentafluorophenyl acrylate) Grafted Surfaces via Hydrazide Conjugation

et al. 2017

View full text Add to dashboard Cite

In this work, we report a convenient and versatile strategy for surface-grafted glycopolymer constructs with the goal of surface modification that controls the chemical presentation and grafting density of carbohydrate side chains. This approach employs a difunctional hydrazine linker, chemically modified to an active ester containing poly(pentafluorophenyl acrylate) grafted scaffold, to conjugate a variety of saccharides through the reducing end. The successive conjugation steps are carried out under mild conditions and yield high surface densities of sugars, as high as 4.8 mnol·cm−2, capable of multivalency, with an intact structure and retained bioactivity. We also demonstrate that this glycosylated surface can bind specific lectins according to the structure of its pendant carbohydrate. To demonstrate bioactivity, this surface platform is used to study the binding events of a human respiratory tract pathogen, Mycoplasma pneumoniae, on surfaces conjugated with sialylated sugars.

show abstract

The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, 99mTc) radiopharmaceuticals

Cited by 29 publications

References 20 publications

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M^I(CO)₃]⁺ (M = Re, ^99mTc) Complexes for Targeting uPAR in Prostate Cancer

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M^I(CO)₃]⁺ (M = Re, ^99mTc) Complexes for Targeting uPAR in Prostate Cancer

A Synthetic Toolbox for the In Situ Formation of Functionalized Homo‐ and Heteropolysaccharide‐Based Hydrogel Libraries

Versatile Methodology for Glycosurfaces: Direct Ligation of Nonderivatized Reducing Saccharides to Poly(pentafluorophenyl acrylate) Grafted Surfaces via Hydrazide Conjugation

Contact Info

Product

Resources

About

The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, 99mTc) radiopharmaceuticals

Cited by 29 publications

References 20 publications

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[MI(CO)3]+ (M = Re, 99mTc) Complexes for Targeting uPAR in Prostate Cancer

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[MI(CO)3]+ (M = Re, 99mTc) Complexes for Targeting uPAR in Prostate Cancer

A Synthetic Toolbox for the In Situ Formation of Functionalized Homo‐ and Heteropolysaccharide‐Based Hydrogel Libraries

Versatile Methodology for Glycosurfaces: Direct Ligation of Nonderivatized Reducing Saccharides to Poly(pentafluorophenyl acrylate) Grafted Surfaces via Hydrazide Conjugation

Contact Info

Product

Resources

About

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M^I(CO)₃]⁺ (M = Re, ^99mTc) Complexes for Targeting uPAR in Prostate Cancer

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M^I(CO)₃]⁺ (M = Re, ^99mTc) Complexes for Targeting uPAR in Prostate Cancer