Engineering Mucin Analogues to Benefit the Mouth Environment

PROJECT SUMMARY. While artificial saliva products are available in the market, they need to replicate natural saliva's essential protective roles in maintaining a healthy oral environment. One of the primary reasons saliva is so beneficial is the presence of mucins, a densely glycosylated protein found in this biological fluid.

Mucins in saliva serve multiple purposes: they provide lubrication during chewing and swallowing, create a protective shield against harmful acids from food and microbes, and play a pivotal role in maintaining the balance of the oral microbiome. However, mucins' intricate structures and functions still need to be fully understood. Factors such as the length of the mucin backbone, the repetitive

nature of its peptide subunits, the specific types of glycan side chains attached, the density of its glycosylation, and the extent of its crosslinking all potentially influence the role of mucins in saliva. Given the pressing need for more effective artificial saliva – ideally containing mucin analogs – this

project aims to create advanced mucin substitutes. This will be achieved through a cycle of informed synthesis based on testing results. The ultimate vision is to custom-design and produce artificial mucins that closely emulate the physiological functions of their natural counterparts found in human

saliva. To achieve this, the project has set specific objectives: (1) Craft artificial mucins that mirror the physicochemical properties of natural salivary mucins, (2) design these mucins to offer protection against tooth demineralization, and (3) fine-tune the glycosylation patterns of these artificial mucins to

ensure they interact optimally with the oral microbiome. The anticipated outcomes of this endeavor are manifold. Firstly, by incorporating these tailor-made mucin analogs into enhanced artificial saliva formulations, we can offer relief to patients afflicted with dry mouth disease. Furthermore, the insights

garnered from this research can pave the way for designing artificial mucins suitable for other mucosal areas impacted by dryness. Lastly, these mucin-inspired therapeutics could serve as targeted modulators or scavenger molecules, intervening with microbial colonization in the human mouth and ensuring a healthy oral environment.