Hydantoanabaenopeptins from Lake Kinneret Microcystis Bloom, Isolation, and Structure Elucidation of the Possible Intermediates in the Anabaenopeptins Biosynthesis
Abstract
:1. Introduction
2. Results and Discussion
3. Material and Methods
3.1. General Experimental Procedure
3.2. Biological Material
3.3. Isolation Procedure
3.4. Physical Data of the Compounds
3.5. Determination of the Absolute Configuration of the Amino Acids by Marfey’s Method [15]
3.6. Protease Inhibition Assays
3.6.1. Trypsin
3.6.2. Chymotrypsin
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compounds | 1 | 2 | 3 | 4 | ||||
---|---|---|---|---|---|---|---|---|
Position | δC | δH | δC | δH | δC | δH | δC | δH |
Tyr/Arg-1 | 174.1, C | 174.6, C | 174.8, C | 174.1, C | ||||
Tyr/Arg-2 | 57.0, CH | 4.34 | 55.9, CH | 4.17 | 56.0, CH | 4.14 | 57.0, CH | 4.35 |
Tyr/Arg-2-NH | 8.55 | 8.69 | 8.74 | 8.55 | ||||
Tyr/Arg-3a Tyr/Arg-3b | 35.5, CH2 | 2.89 2.82 | 28.8, CH2 | 1.73 1.52 | 28.9, CH2 | 1.74 1.52 | 35.5, CH2 | 2.88 2.82 |
Tyr/Arg-4 | 124.3, C | 24.2, CH2 | 1.54 1.45 | 24.2, CH2 | 1.50 1.42 | 124.4, C | ||
Tyr-5,5′/Arg-5 | 130.9, CH | 6.88 | 40.1, CH2 | 3.04 | 40.0, CH2 | 3.05 | 130.9, CH | 6.89 |
Tyr-6,6′/Arg-6 -NH | 115.0, CH | 6.61 | 8.86 | 9.05 | 115.0, CH | 6.61 | ||
Tyr/Arg-7 | 156.7, C | 156.7, C | 157.8, C | 156.6, C | ||||
Arg-7-NH2, NH2+ | 8.43 | 8.03 | ||||||
CO | 156.4, C | 156.9, C | 156.9, C | 156.4, C | ||||
Lys-1 | 167.9, C | 168.2, C | 168.4, C | 168.1, C | ||||
Lys-2 | 56.3, CH | 4.08 | 56.4, CH | 4.30 | 56.5, CH | 4.32 | 56.4, CH | 4.08 |
Lys-3a Lys-3b | 29.3, CH2 | 2.12 0.84 | 29.6, CH2 | 2.40 1.45 | 29.6, CH2 | 2.39 1.45 | 29.3, CH2 | 2.10 0.86 |
Lys-4a Lys-4b | 22.9, CH2 | 1.48 1.37 | 23.1, CH2 | 1.51 1.18 | 23.1, CH2 | 1.45 1.19 | 22.8, CH2 | 1.36 1.00 |
Lys-5a Lys-5b | 28.6, CH2 | 1.37 1.30 | 28.5, CH2 | 1.50 1.40 | 28.3, CH2 | 1.51 1.46 | 28.3, CH2 | 1.39 1.34 |
Lys-6a Lys-6b | 38.4, CH2 | 3.54 2.63 | 38.5, CH2 | 3.55 2.66 | 38.6, CH2 | 3.53 2.66 | 38.5, CH2 | 3.53 2.63 |
Lys-6-NH | 7.41 | 7.43 | 7.46 | 7.41 | ||||
Val/Ile-1 | 172.4, C | 172.4, C | 172.5, C | 172.5, C | ||||
Val/Ile-2 | 57.9, CH | 3.98 | 57.9, CH | 4.09 | 56.4, CH | 4.26 | 56.4, CH | 4.15 |
Val/Ile-2-NH | 7.76 | 7.87 | 7.89 | 7.82 | ||||
Val/Ile-3 | 30.4, CH | 1.96 | 30.5, CH | 2.03 | 36.7, CH | 1.85 | 36.7, CH | 1.79 |
Val/Ile-4 | 19.1, CH3 | 0.96 | 19.1, CH3 | 1.00 | 25.6, CH2 | 1.53 1.15 | 25.5, CH2 | 1.48 1.08 |
Val/Ile-5 | 18.9, CH3 | 0.88 | 18.9, CH3 | 0.94 | 11.8, CH3 | 0.89 | 11.8, CH3 | 0.88 |
Ile-6 | 14.8, CH3 | 0.89 | 14.8, CH3 | 0.84 | ||||
Hty-1 | 171.2, C | 171.1, C | 171.1, C | 171.1, C | ||||
Hty-2 | 48.9, CH | 4.74 | 48.9, CH | 4.77 | 49.0, CH | 4.77 | 49.0, CH | 4.74 |
Hty-2-NH | 8.97 | 8.98 | 8.98 | 8.92 | ||||
Hty-3a Hty-3b | 33.5, CH2 | 1.85 1.73 | 33.4, CH2 | 1.85 1.74 | 33.4, CH2 | 1.85 1.74 | 33.4, CH2 | 1.85 1.72 |
Hty-4a Hty-4b | 30.7, CH2 | 2.60 2.40 | 30.7, CH2 | 2.61 2.42 | 30.8, CH2 | 2.62 2.42 | 30.7, CH2 | 2.59 2.40 |
Hty-5 | 131.0, C | 131.1, C | 131.0, C | 131.1, C | ||||
Hty-6,6′ | 129.2, CH | 6.98 | 129.2, CH | 6.98 | 129.1, CH | 6.98 | 129.2, CH | 6.97 |
Hty-7,7′ | 115.3, CH | 6.66 | 115.3, CH | 6.66 | 115.4, CH | 6.66 | 115.3, CH | 6.65 |
Hty-8 | 155.9, C | 155.8, C | 155.9, C | 155.8, C | ||||
NMe-Ala-1 | 170.0, C | 170.0, C | 170.0, C | 170.0, C | ||||
NMe-Ala-2 | 54.5, CH | 4.85 | 54.6, CH | 4.87 | 54.6, CH | 4.88 | 54.5, CH | 4.85 |
NMe-Ala-3 | 14.1, CH3 | 1.05 | 14.1, CH3 | 1.07 | 14.1, CH3 | 1.07 | 14.1, CH3 | 1.06 |
NMe-Ala-Me | 27.2, CH3 | 1.78 | 27.3, CH3 | 1.79 | 27.3, CH3 | 1.81 | 27.3, CH3 | 1.79 |
Phe-1 | 170.9, C | 171.2, C | 171.3, C | 171.2, C | ||||
Phe-2 | 55.1, CH | 4.34 | 55.1, CH | 4.36 | 55.2, CH | 4.35 | 55.2, CH | 4.35 |
Phe-2-NH | 8.69 | 8.70 | 8.65 | 8.65 | ||||
Phe-3a Phe-3b | 37.7, CH2 | 3.23 2.81 | 37.7, CH2 | 3.23 2.83 | 37.7, CH2 | 3.23 2.84 | 37.7, CH2 | 3.24 2.82 |
Phe-4 | 138.5, C | 138.4, C | 138.5, C | 138.5, C | ||||
Phe-5,5′ | 129.1, CH | 7.06 | 129.0, CH | 7.07 | 129.1, CH | 7.07 | 129.1, CH | 7.07 |
Phe-6,6′ | 128.5, CH | 7.19 | 128.5, CH | 7.19 | 128.4, CH | 7.19 | 128.4, CH | 7.19 |
Phe-7 | 126.3, CH | 7.14 | 126.3, CH | 7.14 | 126.3, CH | 7.14 | 126.3, CH | 7.16 |
Compounds | 5 | 6 | ||
---|---|---|---|---|
Position | δC | δH | δC | δH |
Dht-1 | 174.6, C | 174.0, C | ||
Dht-2 | 53.3, CH | 3.91, m | 56.2, CH | 4.15, m |
Dht-2-NH | 6.27, brd | 8.61, brs | ||
Dht-3a Dht-3b | 32.3, CH2 | 1.61, m 1.50, m | 30.8, CH2 | 1.66, m 1.50, m |
Dht-4a Dht-4b | 27.7, CH2 | 1.48, m 1.45, m | 28.9, CH2 | 1.48, m 1.45, m |
Dht-5 | 34.4, CH2 | 2.40, m | 34.0, CH2 | 2.42, m |
Dht-6 | 132.4, C | 131.6, C | ||
Dht-7,7′ | 129.2, CH | 6.92, d | 129.3, CH | 6.92, d |
Dht-8,8′ | 115.2, CH | 6.63, d | 115.2, CH | 6.65, d |
Dht-9 | 155.4, C | 155.9, C | ||
CO | 157.4, C | 156.9, C | ||
Lys-1 | 172.7, C | 168.4, C | ||
Lys-2 | 55.0, CH | 3.91, ddd | 56.5, CH | 4.31, m |
Lys-2-NH | 6.48, brd | - | ||
Lys-3 | 32.1, CH2 | 1.60, m | 29.6, CH2, | 2.39, m 1.44, m |
Lys-4a Lys-4b | 20.6, CH3 | 1.28, m 1.16, m | 23.1, CH2 | 1.45, m 1.17, m |
Lys-5 | 28.3, CH2 | 1.41, m | 28.6, CH2 | 1.48, m 1.38, m |
Lys-6a Lys-6b | 38.5, CH2 | 3.56, m 2.78, m | 38.5, CH2 | 3.53, m 2.65, m |
Lys-6-NH | 7.14, m | 7.43, t | ||
Val-1 | 172.9, C | 172.4, C | ||
Val-2 | 58.4, CH | 3.88, dd | 57.9, CH | 4.08, t |
Val-2-NH | 7.06, m | 7.88, d | ||
Val-3 | 30.2, CH2 | 1.95, dqq | 30.5, CH | 2.01, m |
Val-4 | 19.6, CH3 | 0.92, d | 19.2, CH3 | 0.99, d |
Val-5 | 19.1, CH3 | 1.02, d | 18.8, CH3 | 0.92, d |
Hty-1 | 171.1, C | 171.2, C | ||
Hty-2 | 48.9, CH | 4.71, dt | 49.0, CH | 4.77, m |
Hty-2-NH | 8.92, d | 8.96, brs | ||
Hty-3a Hty-3b | 33.5, CH2 | 1.85, m 1.70, m | 33.4, CH2 | 1.85, m 1.72, m |
Hty-4a Hty-4b | 30.7, CH2 | 2.62, m 2.41, m | 30.7, CH2 | 2.60, m 2.40, m |
Hty-5 | 131.2, C | 131.0, C | ||
Hty-6,6′ | 129.3, CH | 7.00, d | 129.2, CH | 6.98, d |
Hty-7,7′ | 115.4, CH | 6.65, d | 115.4, CH | 6.66, d |
Hty-8 | 155.8, C | 155.7, C | ||
NMe-Ala-1 | 170.1, C | 170.0, C | ||
NMe-Ala-2 | 54.5, CH | 4.77, q | 54.6, CH | 4.87, q |
NMe-Ala-3 | 14.1, CH3 | 1.05, d | 14.1, CH3 | 1.06, d |
NMe-Ala-Me | 27.3, CH3 | 1.76, s | 27.3, CH3 | 1.79, s |
Phe-1 | 171.2, C | 171.1, C | ||
Phe-2 | 55.2, CH | 4.36, ddd | 55.2, CH | 4.35, ddd |
Phe-2-NH | 8.68, d | 8.69, d | ||
Phe-3a Phe-3b | 37.7, CH2 | 3.30, m 2.77, dd | 37.7, CH2 | 3.23, m 2.81, dd |
Phe-4 | 138.5, C | 138.4, C | ||
Phe-5,5′ | 129.1, CH | 7.05, d | 129.1, CH | 7.07, d |
Phe-6,6′ | 128.5, CH | 7.18, dd | 128.5, CH | 7.19, t |
Phe-7 | 126.3, CH | 7.13, t | 126.3, CH | 7.14, t |
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Weisthal Algor, S.; Sukenik, A.; Carmeli, S. Hydantoanabaenopeptins from Lake Kinneret Microcystis Bloom, Isolation, and Structure Elucidation of the Possible Intermediates in the Anabaenopeptins Biosynthesis. Mar. Drugs 2023, 21, 401. https://doi.org/10.3390/md21070401
Weisthal Algor S, Sukenik A, Carmeli S. Hydantoanabaenopeptins from Lake Kinneret Microcystis Bloom, Isolation, and Structure Elucidation of the Possible Intermediates in the Anabaenopeptins Biosynthesis. Marine Drugs. 2023; 21(7):401. https://doi.org/10.3390/md21070401
Chicago/Turabian StyleWeisthal Algor, Shira, Assaf Sukenik, and Shmuel Carmeli. 2023. "Hydantoanabaenopeptins from Lake Kinneret Microcystis Bloom, Isolation, and Structure Elucidation of the Possible Intermediates in the Anabaenopeptins Biosynthesis" Marine Drugs 21, no. 7: 401. https://doi.org/10.3390/md21070401