Novel post-translational oligomerization of peptidyl dehydrodopa model compound, 1,2-dehydro-N-acetyldopa methyl ester

Evans

Ito

et al. 2020

IJMS

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Melanin is an important phenolic skin pigment found throughout the animal kingdom. Tyrosine and its hydroxylated product dopa provide the starting material for melanin biosynthesis in all animals. Through a set of well-established reactions, they are converted to 5,6-dihydroxyindole (DHI) and DHI-2-carboxylic acid (DHICA). Oxidative polymerization of these two indoles produces the brown to black eumelanin pigment. The steps associated with these transformations are complicated by the extreme instability of the starting materials and the transient and highly reactive nature of the intermediates. We have used mass spectral studies to explore the nonenzymatic mechanism of oxidative transformation of DHI in water. Our results indicate the facile production of not only dimeric and trimeric products but also higher oligomeric forms of DHI upon exposure to air in solution, even under nonenzymatic conditions. Such instantaneous polymerization of DHI avoids toxicity to self-matter and ensures the much-needed deposition of melanin at (a) the wound site and (b) the infection site in arthropods. The rapid deposition of DHI melanin is advantageous for arthropods given their open circulatory system; the process limits blood loss during wounding and prevents the spread of parasites by encapsulating them in melanin, limiting the damage.

Section: Discussionmentioning

confidence: 99%

Nonenzymatic Spontaneous Oxidative Transformation of 5,6-Dihydroxyindole

Evans

Ito

et al. 2020

IJMS

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“…Since radical coupling results in the precipitous loss of semiquinone radicals, in this case, only dimers are formed as shown in Figure 25 [ 91 ]. This kind of dimerization reaction is manifested by a number of dehydro dopyl derivatives [ 26 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ]. The quinone to quinone methide tautomerism is very much in favor of quinone methides in the case of dehydro NADA [ 90 ] as well as 1,2-dehydro- N -acetyldopa [ 26 ].…”

Section: Comparative Oxidation Chemistry Of 12-dehydro- mentioning

confidence: 99%

“…The quinone to quinone methide tautomerism is very much in favor of quinone methides in the case of dehydro NADA [ 90 ] as well as 1,2-dehydro- N -acetyldopa [ 26 ]. However, with 1,2-dehydro- N -acetyldopa methyl ester, quinone product is slightly more stable than the quinone methide [ 94 ]. However, even in this case, the quinone exhibits an ionic Diels–Alder type addition forming the same benzodioxan dimeric products ( Figure 26 ) [ 94 ].…”

Section: Comparative Oxidation Chemistry Of 12-dehydro- mentioning

confidence: 99%

“…However, with 1,2-dehydro- N -acetyldopa methyl ester, quinone product is slightly more stable than the quinone methide [ 94 ]. However, even in this case, the quinone exhibits an ionic Diels–Alder type addition forming the same benzodioxan dimeric products ( Figure 26 ) [ 94 ]. Thus, in dehydro dopa derivatives both the side chain positions seem to be extremely reactive.…”

Section: Comparative Oxidation Chemistry Of 12-dehydro- mentioning

confidence: 99%

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Reactivities of Quinone Methides versus o-Quinones in Catecholamine Metabolism and Eumelanin Biosynthesis

2016

IJMS

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Melanin is an important biopolymeric pigment produced in a vast majority of organisms. Tyrosine and its hydroxylated product, dopa, form the starting material for melanin biosynthesis. Earlier studies by Raper and Mason resulted in the identification of dopachrome and dihydroxyindoles as important intermediates and paved way for the establishment of well-known Raper–Mason pathway for the biogenesis of brown to black eumelanins. Tyrosinase catalyzes the oxidation of tyrosine as well as dopa to dopaquinone. Dopaquinone thus formed, undergoes intramolecular cyclization to form leucochrome, which is further oxidized to dopachrome. Dopachrome is either converted into 5,6-dihydroxyindole by decarboxylative aromatization or isomerized into 5,6-dihydroxyindole-2-carboxylic acid. Oxidative polymerization of these two dihydroxyindoles eventually produces eumelanin pigments via melanochrome. While the role of quinones in the biosynthetic pathway is very well acknowledged, that of isomeric quinone methides, however, remained marginalized. This review article summarizes the key role of quinone methides during the oxidative transformation of a vast array of catecholamine derivatives and brings out the importance of these transient reactive species during the melanogenic process. In addition, possible reactions of quinone methides at various stages of melanogenesis are discussed.

“…The reason for these significant differences between cuticles using NBAD and NADA as sclerotizing precursors remains unknown. In the recent past, we have successfully employed mass spectrometry (MS) to analyze and characterize a number of unusual molecular transformations of catecholamine derivatives that were difficult to delineate by conventional biochemical techniques . In order to tease out the biochemical differences between cuticle using NBAD and cuticle using NADA, we used MS again and report in this paper the novel production of previously uncharacterized colored NBAD quinone adducts.…”

Section: Introductionmentioning

confidence: 99%

Unraveling complex molecular transformations of N‐β‐alanyldopamine that account for brown coloration of insect cuticle

Barek

Evans

Rapid Comm Mass Spectrometry

2017

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LC/MS analysis of the reaction mixture of NBAD-cuticular enzyme reactions reveals the novel production of colored quinone adducts that are not possible for NADA. Therefore, our results suggest that the brown coloration of cuticle formed through NBAD crosslinking is likely due to the formation and accumulation of NBAD quinone and its adducts, while NADA quinone adducts tend not to form during NADA crosslinking, producing a nearly colorless cuticle.