Browsing by Author "Laronha, Helena"
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- Challenges in matrix metalloproteinases inhibitionPublication . Laronha, Helena; Carpinteiro, Inês; Portugal, Jaime; Azul, Ana; Polido, Mário; Petrova, Krasimira T.; Salema-Oom, Madalena; Caldeira, JorgeMatrix metalloproteinases are enzymes that degrade the extracellular matrix. They have different substrates but similar structural organization. Matrix metalloproteinases are involved in many physiological and pathological processes and there is a need to develop inhibitors for these enzymes in order to modulate the degradation of the extracellular matrix (ECM). There exist two classes of inhibitors: endogenous and synthetics. The development of synthetic inhibitors remains a great challenge due to the low selectivity and specificity, side effects in clinical trials, and instability. An extensive review of currently reported synthetic inhibitors and description of their properties is presented.
- Challenges in matrix metalloproteinases inhibitionPublication . Laronha, Helena; Carpinteiro, Inês; Portugal, Jaime; Azul, Ana; Polido, Mário; Petrova, Krasimira T.; Salema-Oom, Madalena; Caldeira, JorgeMatrix metalloproteinases are enzymes that degrade the extracellular matrix. They have different substrates but similar structural organization. Matrix metalloproteinases are involved in many physiological and pathological processes and there is a need to develop inhibitors for these enzymes in order to modulate the degradation of the extracellular matrix (ECM). There exist two classes of inhibitors: endogenous and synthetics. The development of synthetic inhibitors remains a great challenge due to the low selectivity and specificity, side effects in clinical trials, and instability. An extensive review of currently reported synthetic inhibitors and description of their properties is presented.
- Polymerizable matrix metalloproteinases’ inhibitors with potential application for dental restorationsPublication . Laronha, Helena; Carpinteiro, Inês; Portugal, Jaime; Azul, Ana; Polido, Mário; Petrova, Krasimira T.; Salema-Oom, Madalena; Barahona, Isabel; Caldeira, JorgeCollagen cleavage by matrix metalloproteinase (MMP) is considered a major cause of dental resins long term failure. Most MMP inhibitors display significant toxicity and are unsuitable for dental resins’ applications. Here we report a study of a new class of inhibitors that display the unique property of being co-polymerizable with other vinyl compounds present in commercial dental resins, limiting their release and potential toxicity. Computational affinity towards the active site of different MMP-1; -2; -8; -9 and -13 of several compounds showed interesting properties and were synthesized. These free compounds were tested concerning their toxicity upon contact with two different cell types, with no substantial decrease in cell viability at high concentrations. Even so, compound’s safety can be further improved upon copolymerization with commercial dental resins, limiting their release.
- Structure and function of human matrix metalloproteinasesPublication . Laronha, Helena; Caldeira, JorgeThe extracellular matrix (ECM) is a macromolecules network, in which the most abundant molecule is collagen. This protein in triple helical conformation is highly resistant to proteinases degradation, the only enzymes capable of degrading the collagen are matrix metalloproteinases (MMPs). This resistance and maintenance of collagen, and consequently of ECM, is involved in several biological processes and it must be strictly regulated by endogenous inhibitors (TIMPs). The deregulation of MMPs activity leads to development of numerous diseases. This review shows MMPs complexity.