Major Gooyit
University of Notre Dame
ProdrugMatrix metalloproteinaseChemistryStructure–activity relationshipMatrix metalloproteinase inhibitorGelatinaseThiiraneBlood–brain barrierOnchocerca volvulusWound healingChitinaseTraumatic brain injuryGelatinasesMoultingCentral nervous systemBiochemistryStereochemistryMedicineBiologyMicrobiologyPharmacology
Publications 23
#1Trung T. Nguyen (ND: University of Notre Dame)H-Index: 5
#2William R. Wolter (ND: University of Notre Dame)H-Index: 21
Last. Mayland Chang (ND: University of Notre Dame)H-Index: 33
view all 8 authors...
Matrix metalloproteinases (MMPs) play important roles in wound healing, but attribution of their functions in repair of wounds has been challenging. Commonly used tools such as MMP-knockout mice an...
1 CitationsSource
#1Major Gooyit (Scripps Research Institute)H-Index: 13
#2Pedro O. Miranda (Scripps Research Institute)H-Index: 16
Last. Kim D. Janda (Scripps Research Institute)H-Index: 92
view all 5 authors...
Active vaccination examining a single hapten engendered with a series of peptidic linkers has resulted in the production of antimethamphetamine antibodies. Given the limited chemical complexity of methamphetamine, the structure of the linker species embedded within the hapten could have a substantial effect on the ultimate efficacy of the resulting vaccines. Herein, we investigate linker effects by generating a series of methamphetamine haptens that harbor a linker with varying amino acid identi...
19 CitationsSource
#1Charles Marusak (Case Western Reserve University)H-Index: 1
#2Ian Bayles (Case Western Reserve University)H-Index: 5
Last. Barbara Bedogni (Case Western Reserve University)H-Index: 12
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Abstract MT1-MMP and MMP2 have been implicated as pro-tumorigenic and pro-metastatic factors in a wide variety of cancers including melanoma. We have previously demonstrated that MT1-MMP is highly expressed in melanoma where it promotes melanoma cell invasion and metastasis in part through the activation of its target MMP2. Given the accessibility of MMPs, as they are either secreted ( e.g. MMP2) or membrane-tethered ( e.g. MT1-MMP), they represent ideal targets for specific inhibition via small...
16 CitationsSource
#1Major Gooyit (Scripps Research Institute)H-Index: 13
#2Kim D. Janda (Scripps Research Institute)H-Index: 92
Prolonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this stud...
27 CitationsSource
#1Major Gooyit (Scripps Research Institute)H-Index: 13
#2Kim D. Janda (Scripps Research Institute)H-Index: 92
Cysteine protease Cwp84 is responsible for surface-layer processing in Clostridium difficile and was also shown to cleave several human extracellular matrix components in vitro. To enable the facile identification and characterization of Cwp84 inhibitors, we developed a fluorogenic 10-mer peptide based on the enzyme’s natural substrate SlpA that is amenable for use in FRET-based high-throughput screening. The design of substrate-mimetic inhibitors led to epoxysuccinate 8c, which displayed an ina...
2 CitationsSource
#1Kyoji Tsuchikama (Scripps Research Institute)H-Index: 19
#2Major Gooyit (Scripps Research Institute)H-Index: 13
Last. Kim D. Janda (Scripps Research Institute)H-Index: 92
view all 7 authors...
Reported herein is that (4S)-4,5-dihydroxy-2,3-pentanedione (DPD) can undergo a previously undocumented non-enzymatic glycation reaction. Incubation of DPD with viral DNA or the antibiotic gramicidin S resulted in significant biochemical alterations. A protein-labeling method was consequently developed that facilitated the identification of unrecognized glycation targets of DPD in a prokaryotic system. These results open new avenues toward tracking and understanding the fate and function of the ...
1 CitationsSource
#1Ming Gao (ND: University of Notre Dame)H-Index: 11
#2Trung T. Nguyen (ND: University of Notre Dame)H-Index: 5
Last. Mayland Chang (ND: University of Notre Dame)H-Index: 33
view all 7 authors...
Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body’s res...
77 CitationsSource
#1Bridgette D. Semple (University of Melbourne)H-Index: 26
#2Linda J. Noble-Haeusslein (UCSF: University of California, San Francisco)H-Index: 38
Last. Alpa Trivedi (UCSF: University of California, San Francisco)H-Index: 14
view all 11 authors...
The gelatinases, matrix metalloproteinases (MMP)-2 and MMP-9, are thought to be key mediators of secondary damage in adult animal models of brain injury. Moreover, an acute increase in these proteases in plasma and brain extracellular fluid of adult patients with moderate-to-severe traumatic brain injuries (TBIs) is associated with poorer clinical outcomes and mortality. Nonetheless, their involvement after TBI in the pediatric brain remains understudied. Using a murine model of TBI at postnatal...
13 CitationsSource
#1Major GooyitH-Index: 13
#2Zhihong PengH-Index: 13
Last. Mayland ChangH-Index: 33
view all 4 authors...
The gelatinases (matrix metalloproteinase (MMP)-2 and MMP-9) play important roles in the pathophysiology of several diseases, including cancer metastases, neurological diseases, and chronic wounds. MMPs also mediate beneficial repair and recovery functions. Thus, the use of selective MMP inhibitors is required to avoid side effects. The prototype gelatinase inhibitor SB-3CT displays potency and selectivity towards the gelatinases. SB-3CT contains a thiirane ring that involves a reaction catalyze...
2 CitationsSource
#1Mijoon Lee (ND: University of Notre Dame)H-Index: 29
#2Zhenzhou Chen (MU: University of Missouri)H-Index: 5
Last. Mayland Chang (ND: University of Notre Dame)H-Index: 33
view all 16 authors...
SB-3CT is a potent and selective inhibitor of matrix metalloproteinase (MMP)-2 and -9, which has shown efficacy in an animal model of severe traumatic brain injury (TBI). However, SB-3CT is poorly water-soluble and is metabolized primarily to p-hydroxy SB-3CT (2), a more potent inhibitor than SB-3CT. We synthesized the O-phosphate prodrug (3) of compound 2 to enhance its water solubility by more than 2000-fold. The prodrug 3 was a poor MMP inhibitor, but readily hydrolyzed to the active 2 in hum...
15 CitationsSource