This is a good study carried out by one of the world's leading laboratories in the development of cyclic peptides. The study is rigorously detailed, as indicated by its publication in one of the most important journals in the field of chemistry.

Peptides are very small proteins. There are many drugs based on peptides and proteins. However, peptides and proteins do not reach the blood orally because they are degraded during digestion. This paper describes a new method to develop cyclized peptides that can reach the blood orally and through intestinal absorption. There are many methods of peptide cyclization and combinatorial chemistry, but it appears that this strategy has identified peptides that reach the blood with high efficiency, up to 18% of the administered dose.  

For the time being, only one peptide has been developed with this platform against a therapeutic target for which alternatives already exist. To test whether this method will be truly transformative, it will be necessary to wait for the development of peptides against other targets of interest.

The work is of high quality, they are looking for cyclic structures that are stable to the conditions of our stomach and that can also be absorbed in the intestinal tract. To do this, they use a method known as combinatorial chemistry, in which they are able to synthesise a wide variety of cyclic compounds on a very small scale and evaluate their biological activity. They then further refine these structures to improve aspects such as intestinal absorption, oxidation, etc., thereby improving their properties. What is relevant is that they start using a very simple and selective cyclisation method and later replace it with another that provides greater stability to the compounds prepared, without apparently interfering with their activity. A very well planned and developed study, using a therapeutic target in which this group is an expert.  

Much of the biological and structural aspects used in this work are already known. The most relevant is to use robust chemical methods to fix the molecules to be studied (small peptides) in a certain form that increases their stability while also improving their thrombin inhibition activity. It involves a technology that allows synthesis to be done on a very small scale and without the need for time-consuming and labour-intensive purification steps (researchers performing such a technique routinely), so that some of their most relevant biological properties (in this case thrombin inhibition activity and permeability) can be quickly determined. The method described can be used to search for other therapeutic targets in which the activity of the molecules can be evaluated and improved at the same time as their absorption in the intestinal tract.   

I don't think the work opens a new era, what it does bring is a new alternative in the development of active molecules derived from small peptides that are permeable (that can be administered orally), something that has not been easy with this type of molecule so far. The possibility of being able to use small peptides that can be administered orally does represent an important leap forward in the development of new drugs. Until now, small peptides have not been used for this purpose, due to their low permeability in our intestine and, moreover, their low stability in the highly acidic conditions of our stomach. Although it was already known that the stability of peptides could be improved by preparing cyclic derivatives, in this case they show that their oral use can be improved. I believe that to speak of a "new era" is somewhat exaggerated, although this does not detract from the quality of the work and the potential that this strategy may have in the future, which, of course, must be demonstrated in future studies.