Solid-Phase Synthesis and Kinetic Characterization of Fluorogenic Enzyme-Degradable Hydrogel Cross-linkers

Moss, Jason A.; Stokols, Shula; Hixon, Mark S.; Ashley, Fawn T.; Chang, Jason Y. H.; Janda, Kim D.

doi:10.1021/bm051001s

Cited by 20 publications

(11 citation statements)

References 35 publications

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“…[22,23] One potential solution to the inability to predict physical behavior is the generation of a higher-throughput approach to rapidly synthesize and screen photopolymerizable libraries of biomaterials. Combinatorial polymer synthesis has been previously performed by numerous investigators [24][25][26][27] and has led to the identification of polymers with unique properties. However, this has not been previously performed for the synthesis of photoreactive macromers that form crosslinked and degradable polymers.…”

mentioning

confidence: 99%

A Combinatorial Library of Photocrosslinkable and Degradable Materials

Anderson¹,

Tweedie²,

Hossain³

et al. 2006

Advanced Materials

137

191

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Photocrosslinkable and degradable polymers are finding a broad range of applications as drug-delivery vehicles, tissueengineering scaffolds, and in the fabrication of microdevices. [1][2][3] However, the synthesis of multifunctional macromers that form these degradable networks commonly involves multiple functionalization and purification steps, which makes the development of large numbers of polymers with diverse properties difficult. Here, we develop the first combinatorial library of degradable photocrosslinked materials. A library of acrylate-terminated poly(b-amino ester)s was synthesized in parallel via a condensation reaction that combines primary or secondary amines with diacrylates. This library of macromers was then photopolymerized to form degradable networks, with a wide range of degradation times (< 1 day to minimal mass loss after three months), mass-loss profiles, and mechanical properties (∼ 4 to 350 MPa). We believe this library approach will allow for the rapid screening and design of degradable polymers for a variety of applications. The spatial and temporal control afforded during photoinitiated polymerizations has motivated their wide application in the general field of biomaterials. [1,2] For example, photocrosslinkable hydrogels are used for the delivery of cells to injured tissues, [4][5][6][7][8] for the encapsulation and controlled delivery of biological molecules, [9][10][11] and for controlled fluid flow and cell confinement in microfluidics. [12,13] Additionally, highly crosslinked photopolymers are currently used in dentistry [14] and are being developed as bone-replacement materials [15,16] and for the fabrication of microdevices.[17] Many of these applications are only possible owing to the controlled nature of this type of polymerization. For example, photoinitiated control of polymerization allows for their application as injectable biomaterials [18,19] with a non-cytotoxic polymerization process.[20]Additionally, through use of masks and lasers, the spatial control of the polymerization process allows for unique patterning and construction of complex materials.[21]Numerous photopolymerizable and degradable materials have been developed, including polyanhydrides, poly(propylene fumarates), poly(ethylene glycol), and polysaccharides, [8,15,16,18] all utilizing multiple reaction and purification steps for synthesis of the photopolymerizable precursors. Despite this work, it has proven challenging to predict specific desirable properties (e.g., degradation and mechanics) from known chemical and structural details of the network precursors. These properties are essential in the design of degradable polymers. For instance, it may be desirable to synthesize a very hard material for some applications (e.g., orthopaedics), whereas a soft material is advantageous for other applications (e.g., tissue adhesive). [22,23] One potential solution to the inability to predict physical behavior is the generation of a higher-throughput approach to rapidly synthesize and screen photopolymerizable li...

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mentioning

confidence: 99%

A Combinatorial Library of Photocrosslinkable and Degradable Materials

Anderson¹,

Tweedie²,

Hossain³

et al. 2006

Advanced Materials

137

191

View full text Add to dashboard Cite

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“…(Moss et al, 2006). Work performed by Denmeade et al initially studied a range of peptide sequences to determine cleavage rate as well as specificity (Denmeade et al, 2003; Denmeade et al, 1997; Denmeade et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…This synthesis scheme was similar to that reported by Moss et al . (Moss et al, 2006). Ultimately, the two bis-methacrylamide peptide crosslinkers GISSQ↓YSSK ( QY ) and GISSF↓YSSK ( FY ) were synthesized to investigate the impact on degradation rate of either a Q or F residue in the P 2 position.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic triggered release of an HIV-1 entry inhibitor from prostate specific antigen degradable microparticles

Clark¹,

Aliyar²,

Lee³

et al. 2011

International Journal of Pharmaceutics

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This paper describes the design, construction and characterization of the first anti-HIV drug delivery system that is triggered to release its contents in the presence of human semen. Microgel particles were synthesized with a crosslinker containing a peptide substrate for the seminal serine protease prostate specific antigen (PSA) and were loaded with the HIV-1 entry inhibitor sodium poly(styrene-4-sulfonate) (pSS). The particles were composed of N-2-hydroxyproplymethacrylamide and bis-methacrylamide functionalized peptides based on the PSA substrates GISSFYSSK and GISSQYSSK. Exposure to human seminal plasma (HSP) degraded the microgel network and triggered the release of the entrapped antiviral polymer. Particles with the crosslinker composed of the substrate GISSFYSSK showed 17 times faster degradation in seminal plasma than that of the crosslinker composed of GISSQYSSK. The microgel particles containing 1 mol% GISSFYSSK peptide crosslinker showed complete degradation in 30 hours in the presence of HSP at 37 °C and pSS released from the microgels within 30 minutes reached a concentration of 10 µg/mL, equivalent to the published IC90 for pSS. The released pSS inactivated HIV-1 in the presence of HSP. The solid phase synthesis of the crosslinkers, preparation of the particles by inverse microemulsion polymerization, HSP-triggered release of pSS and inactivation of HIV-1 studies are described.

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“…The alloc group is removed using a catalytic amount of the soluble, air-stable catalyst tetrakis(triphenylphosphine)palladium(0) (Pd(PPh 3 ) 4 ), in combination with an allyl scavenger such as 1,3-dimethylbarbituric acid in DMF [96]. These conditions are compatible with all standard protecting groups and peptide-resin linkages, and are both generally applicable and scalable.…”

Section: Amine Protecting Groupsmentioning

confidence: 99%

Design of Peptide Imaging Agents for Whole-body and Intraoperative Molecular Imaging

Moss¹,

Vāvere²,

Azhdarinia³

2012

curr med chem

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Due to the growing toolkit of targeted contrast agents, molecular imaging continues to play a prominent role in the clinical care of cancer. Peptide-based imaging approaches are of particular significance due to their favorable pharmacokinetic properties, established manufacturing infrastructure, and documented clinical success in whole-body imaging. A logical extension of molecular imaging with peptides is to improve surgical outcomes in cancer through highly sensitive and specific probes which can be used intraoperatively. Advances in fluorescent imaging have resulted in various peptide labeling strategies with intraoperative indications. In this review, we focused on the evolving design of peptide imaging agents starting with the clinically used somatostatin targeting peptides. We then review the current synthetic approaches used for dual-labeled agent development and offer perspectives on optimal protection schemes that can be used for multimodal probe development.

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Solid-Phase Synthesis and Kinetic Characterization of Fluorogenic Enzyme-Degradable Hydrogel Cross-linkers

Cited by 20 publications

References 35 publications

A Combinatorial Library of Photocrosslinkable and Degradable Materials

A Combinatorial Library of Photocrosslinkable and Degradable Materials

Enzymatic triggered release of an HIV-1 entry inhibitor from prostate specific antigen degradable microparticles

Design of Peptide Imaging Agents for Whole-body and Intraoperative Molecular Imaging

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