Microbiological Aspects of Unique, Rare, and Unusual Fatty Acids Derived from Natural Amides and Their Pharmacological Profile
Round 1
Reviewer 1 Report
The paper of V. Dembitsky reviews the pharmacology profile of peptides-derived unusual fatty acids from microorganism origin. These fatty acids are unusual compounds that the existence and activities of which are important to remind the community (both pharmacologists and medicinal chemists) as they remain largely unexplored analogue-wise.
The paper is a long descriptive list of natural compounds with their pharmacological activities. I find this kind of reviews important because the data are scattered throughout the literature, and too often difficult to reach to have a global picture of the domain. Thus, I encourage this kind of approach.
The iconography is nice and helpful.
The figure 3 (and the other similar ones) construction should be a bit detailed.
The table 1 needs to be fixed: compound “1”, “2” and “Fa V” need clarifications. At least a bit of explanation (is 1 derived from the compound FR just above?) even if already mentioned in the text. Alternatively, a mention should be put somewhere in the beginning of the table, mentioning that the compounds are depicted in the corresponding table. The same applies for all other tables.
The review seems to be complete, or at least a large panel of compounds is presented.
On the scientific side, I would like to point that a couple of sentences should be added on the stability of some of those compounds. It would be very surprising that some were not reported for their metabolic stability. Mention (and discussion) should be done of it, as it represents one of the reasons why medicinal chemist – at least in Industry – are not keen to work on both fatty acids and pseudopeptides. A discussion exists on these (peptide) stabilities and may be worth mentioning (doi: 10.1002/pro.3601). I have no idea if the same exists on fatty acids.
Minor:
The sentence lines 39-40 is obscure.
This said, the paper itself should be corrected by an English native speaker, as some sentences are awkward and should be fixed. This said, this observation tends to disappear while progressing in the paper. Maybe just a couple of things to correct in the very beginning of the review.
Furthermore, I urge the writer to pay attention to details (such as double space changed in mono space and back again) as well as providing a personal comment on the finding(s). For example, the first paragraph of section 2 (lines 52-57) does not comment the findings, as in what these compounds are different, important, and promising ones. The essence of review(s) is to give the personal feelings of the writer.
Author Response
Reviewer 1
The author is very grateful to Reviewer 1 for the positive feedback on my article. All comments and wishes expressed by Reviewer 1 are corrected directly in the text and highlighted in blue.
The paper of V. Dembitsky reviews the pharmacology profile of peptides-derived unusual fatty acids from microorganism origin. These fatty acids are unusual compounds that the existence and activities of which are important to remind the community (both pharmacologists and medicinal chemists) as they remain largely unexplored analogue-wise.
The paper is a long descriptive list of natural compounds with their pharmacological activities. I find this kind of reviews important because the data are scattered throughout the literature, and too often difficult to reach to have a global picture of the domain. Thus, I encourage this kind of approach.
The iconography is nice and helpful.
The figure 3 (and the other similar ones) construction should be a bit detailed.
To build 3D graphs of the biological activity of fatty acids from natural pseudopeptides, a proprietary computer program OriginPro 2021 was used, into which data were entered from another computer program PASS, which calculates the degree of reliability of biological activity.
The table 1 needs to be fixed: compound “1”, “2” and “Fa V” need clarifications. At least a bit of explanation (is 1 derived from the compound FR just above?) even if already mentioned in the text. Alternatively, a mention should be put somewhere in the beginning of the table, mentioning that the compounds are depicted in the corresponding table. The same applies for all other tables.
Additions made to the table and text
The review seems to be complete, or at least a large panel of compounds is presented.
On the scientific side, I would like to point that a couple of sentences should be added on the stability of some of those compounds. It would be very surprising that some were not reported for their metabolic stability. Mention (and discussion) should be done of it, as it represents one of the reasons why medicinal chemist – at least in Industry – are not keen to work on both fatty acids and pseudopeptides. A discussion exists on these (peptide) stabilities and may be worth mentioning (doi: 10.1002/pro.3601). I have no idea if the same exists on fatty acids.
In connection with the comments, I completely changed the Introduction, and added new literature (see References 1,3,4,5 and 6).
Minor:
The sentence lines 39-40 is obscure.
This said, the paper itself should be corrected by an English native speaker, as some sentences are awkward and should be fixed. This said, this observation tends to disappear while progressing in the paper. Maybe just a couple of things to correct in the very beginning of the review.
Furthermore, I urge the writer to pay attention to details (such as double space changed in mono space and back again) as well as providing a personal comment on the finding(s). For example, the first paragraph of section 2 (lines 52-57) does not comment the findings, as in what these compounds are different, important, and promising ones. The essence of review(s) is to give the personal feelings of the writer.
The text says that these fatty acids in FA amides demonstrate strong antifungal activity.
Once again, I want to thank you for your real help and adequate attitude to both the article and the author.
Sincerely yours
Valery Dembitsky
Author Response File: 
Author Response.pdf
Reviewer 2 Report
1. Title: "Microbiological aspects of unique, rare and unusual fatty acids derived from natural pseudopeptides and their pharmacological profile"
Pseudopeptides are defined as amides of amino acids that do not occur naturally in peptides or proteins, especially polypeptides. The compounds shown in Figure 1 do not meet this definition. They are amides of unusual fatty acids. The fatty acids are not attached to pseudopeptides. This needs to be clarified throughout the manuscript. Are any or some of the fatty acids shown in other figures amide-linked to pseudopeptides?
2. 1st sentence of the Introduction: "Natural and/or synthetic pseudopeptides are surregates of the amide bond and it are analogues of peptides or peptide hormones and have many potential pharmacological applications, as it's had different biological activity, or enzyme inhibitors.
Perhaps: There is no need to mention synthetic pseudopeptides.
... pseudopeptides are surregates of the amide bond ... This makes no sense.
Pseudopeptides are analogues of peptides or peptide hormones. They have a variety of biological activities, including enzyme inhibition, that have many potential pharmacological applications.
The language is no all this bad, but it needs improvement throughout the manuscript. If you do not have a colleague willing to help with this, MDPI does provide a language editing service.
3. Line 52: " ... (1, structure see in Fig 1) The structures in Figure 1 are not numbered.
4. line 78: What is PASS?
5. Line 79: How can something hace antifungal activity with 95% confidence?
6. Figures 2, 5, 12, 15 and 26 need size bars.
7. What are 1 & 2? What are the numbers in parentheses? References should be cited here. This pertains to the other tables as well
Author Response
Reviewer 2
Dear Reviewer 2, I fully agree with your comments and wishes. I completely redid the article and removed Pseudopeptides from the title. So it will be quite realistic and correct.
In connection with the comments, I completely changed the Introduction, and changed the literature.
All changes in the text are highlighted in blue.
Comments and Suggestions for Authors
- Title: "Microbiological aspects of unique, rare and unusual fatty acids derived from natural pseudopeptides and their pharmacological profile"
Pseudopeptides are defined as amides of amino acids that do not occur naturally in peptides or proteins, especially polypeptides. The compounds shown in Figure 1 do not meet this definition. They are amides of unusual fatty acids. The fatty acids are not attached to pseudopeptides. This needs to be clarified throughout the manuscript. Are any or some of the fatty acids shown in other figures amide-linked to pseudopeptides?
- 1st sentence of the Introduction: "Natural and/or synthetic pseudopeptides are surregates of the amide bond and it are analogues of peptides or peptide hormones and have many potential pharmacological applications, as it's had different biological activity, or enzyme inhibitors.
Perhaps: There is no need to mention synthetic pseudopeptides.
... pseudopeptides are surregates of the amide bond ... This makes no sense.
Pseudopeptides are analogues of peptides or peptide hormones. They have a variety of biological activities, including enzyme inhibition, that have many potential pharmacological applications.
The language is no all this bad, but it needs improvement throughout the manuscript. If you do not have a colleague willing to help with this, MDPI does provide a language editing service.
- Line 52: " ... (1, structure see in Fig 1) The structures in Figure 1 are not numbered.
Corrected.
- line 78: What is PASS?
Corrected.
- Line 79: How can something hace antifungal activity with 95% confidence?
Corrected. See Fig. 3
- Figures 2, 5, 12, 15 and 26 need size bars.
Unfortunately, I cannot make size bars, this is a very long and painstaking work. You can delete all these drawings if you think it's important.
- What are 1 & 2? What are the numbers in parentheses? References should be cited here. This pertains to the other tables as well.
Corrected.
Once again, I want to thank you for your real help and adequate attitude to both the article and the author.
Sincerely yours
Valery Dembitsky
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
OK
